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17.5: Viruses - Biology

17.5: Viruses - Biology


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No one knows exactly when viruses emerged or from where they came, since viruses do not leave historical footprints such as fossils. Modern viruses are thought to be a mosaic of bits and pieces of nucleic acids picked up from various sources along their respective evolutionary paths. Viruses are acellular, parasitic entities that are not classified within any domain because they are not considered alive. They have no plasma membrane, internal organelles, or metabolic processes, and they do not divide. Instead, they infect a host cell and use the host’s replication processes to produce progeny virus particles. Viruses infect all forms of organisms including bacteria, archaea, fungi, plants, and animals. Living things grow, metabolize, and reproduce. Viruses replicate, but to do so, they are entirely dependent on their host cells. They do not metabolize or grow, but are assembled in their mature form.

Viruses are diverse. They vary in their structure, their replication methods, and in their target hosts or even host cells. While most biological diversity can be understood through evolutionary history, such as how species have adapted to conditions and environments, much about virus origins and evolution remains unknown.

How Viruses Replicate

Viruses were first discovered after the development of a porcelain filter, called the Chamberland-Pasteur filter, which could remove all bacteria visible under the microscope from any liquid sample. In 1886, Adolph Meyer demonstrated that a disease of tobacco plants, tobacco mosaic disease, could be transferred from a diseased plant to a healthy one through liquid plant extracts. In 1892, Dmitri Ivanowski showed that this disease could be transmitted in this way even after the Chamberland-Pasteur filter had removed all viable bacteria from the extract. Still, it was many years before it was proven that these “filterable” infectious agents were not simply very small bacteria but were a new type of tiny, disease-causing particle.

Virions, single virus particles, are very small, about 20–250 nanometers (1 nanometer = 1/1,000,000 mm). These individual virus particles are the infectious form of a virus outside the host cell. Unlike bacteria (which are about 100 times larger), we cannot see viruses with a light microscope, with the exception of some large virions of the poxvirus family (Figure 17.1.2).

It was not until the development of the electron microscope in the 1940s that scientists got their first good view of the structure of the tobacco mosaic virus (Figure) and others. The surface structure of virions can be observed by both scanning and transmission electron microscopy, whereas the internal structures of the virus can only be observed in images from a transmission electron microscope (Figure 17.1.3).

The use of this technology has allowed for the discovery of many viruses of all types of living organisms. They were initially grouped by shared morphology, meaning their size, shape, and distinguishing structures. Later, groups of viruses were classified by the type of nucleic acid they contained, DNA or RNA, and whether their nucleic acid was single- or double-stranded. More recently, molecular analysis of viral replication cycles has further refined their classification.

A virion consists of a nucleic-acid core, an outer protein coating, and sometimes an outer envelope made of protein and phospholipid membranes derived from the host cell. The most visible difference between members of viral families is their morphology, which is quite diverse. An interesting feature of viral complexity is that the complexity of the host does not correlate to the complexity of the virion. Some of the most complex virion structures are observed in bacteriophages, viruses that infect the simplest living organisms, bacteria.

Viruses come in many shapes and sizes, but these are consistent and distinct for each viral family (Figure 17.1.4). All virions have a nucleic-acid genome covered by a protective layer of protein, called a capsid. The capsid is made of protein subunits called capsomeres. Some viral capsids are simple polyhedral “spheres,” whereas others are quite complex in structure. The outer structure surrounding the capsid of some viruses is called the viral envelope. All viruses use some sort of glycoprotein to attach to their host cells at molecules on the cell called viral receptors. The virus exploits these cell-surface molecules, which the cell uses for some other purpose, as a way to recognize and infect specific cell types. For example, the measles virus uses a cell-surface glycoprotein in humans that normally functions in immune reactions and possibly in the sperm-egg interaction at fertilization. Attachment is a requirement for viruses to later penetrate the cell membrane, inject the viral genome, and complete their replication inside the cell.

The T4 bacteriophage, which infects the E. coli bacterium, is among the most complex virion known; T4 has a protein tail structure that the virus uses to attach to the host cell and a head structure that houses its DNA.

Adenovirus, a nonenveloped animal virus that causes respiratory illnesses in humans, uses protein spikes protruding from its capsomeres to attach to the host cell. Nonenveloped viruses also include those that cause polio (poliovirus), plantar warts (papillomavirus), and hepatitis A (hepatitis A virus). Nonenveloped viruses tend to be more robust and more likely to survive under harsh conditions, such as the gut.

Enveloped virions like HIV (human immunodeficiency virus), the causative agent in AIDS (acquired immune deficiency syndrome), consist of nucleic acid (RNA in the case of HIV) and capsid proteins surrounded by a phospholipid bilayer envelope and its associated proteins (Figure 17.1.4). Chicken pox, influenza, and mumps are examples of diseases caused by viruses with envelopes. Because of the fragility of the envelope, nonenveloped viruses are more resistant to changes in temperature, pH, and some disinfectants than enveloped viruses.

Overall, the shape of the virion and the presence or absence of an envelope tells us little about what diseases the viruses may cause or what species they might infect, but is still a useful means to begin viral classification.

ART CONNECTION

Which of the following statements about virus structure is true?

  1. All viruses are encased in a viral membrane.
  2. The capsomere is made up of small protein subunits called capsids.
  3. DNA is the genetic material in all viruses.
  4. Glycoproteins help the virus attach to the host cell.

Unlike all living organisms that use DNA as their genetic material, viruses may use either DNA or RNA as theirs. The virus core contains the genome or total genetic content of the virus. Viral genomes tend to be small compared to bacteria or eukaryotes, containing only those genes that code for proteins the virus cannot get from the host cell. This genetic material may be single-stranded or double-stranded. It may also be linear or circular. While most viruses contain a single segment of nucleic acid, others have genomes that consist of several segments.

DNA viruses have a DNA core. The viral DNA directs the host cell’s replication proteins to synthesize new copies of the viral genome and to transcribe and translate that genome into viral proteins. DNA viruses cause human diseases such as chickenpox, hepatitis B, and some venereal diseases like herpes and genital warts.

RNA viruses contain only RNA in their cores. To replicate their genomes in the host cell, the genomes of RNA viruses encode enzymes not found in host cells. RNA polymerase enzymes are not as stable as DNA polymerases and often make mistakes during transcription. For this reason, mutations, changes in the nucleotide sequence, in RNA viruses occur more frequently than in DNA viruses. This leads to more rapid evolution and change in RNA viruses. For example, the fact that influenza is an RNA virus is one reason a new flu vaccine is needed every year. Human diseases caused by RNA viruses include hepatitis C, measles, and rabies.

Viruses can be seen as obligate intracellular parasites. The virus must attach to a living cell, be taken inside, manufacture its proteins and copy its genome, and find a way to escape the cell so the virus can infect other cells and ultimately other individuals. Viruses can infect only certain species of hosts and only certain cells within that host. The molecular basis for this specificity is that a particular surface molecule, known as the viral receptor, must be found on the host cell surface for the virus to attach. Also, metabolic differences seen in different cell types based on differential gene expression are a likely factor in which cells a virus may use to replicate. The cell must be making the substances the virus needs, such as enzymes the virus genome itself does not have genes for, or the virus will not be able to replicate using that cell.

Steps of Virus Infections

A virus must “take over” a cell to replicate. The viral replication cycle can produce dramatic biochemical and structural changes in the host cell, which may cause cell damage. These changes, called cytopathic effects, can change cell functions or even destroy the cell. Some infected cells, such as those infected by the common cold virus (rhinovirus), die through lysis (bursting) or apoptosis (programmed cell death or “cell suicide”), releasing all the progeny virions at once. The symptoms of viral diseases result from the immune response to the virus, which attempts to control and eliminate the virus from the body, and from cell damage caused by the virus. Many animal viruses, such as HIV (human immunodeficiency virus), leave the infected cells of the immune system by a process known as budding, where virions leave the cell individually. During the budding process, the cell does not undergo lysis and is not immediately killed. However, the damage to the cells that HIV infects may make it impossible for the cells to function as mediators of immunity, even though the cells remain alive for a period of time. Most productive viral infections follow similar steps in the virus replication cycle: attachment, penetration, uncoating, replication, assembly, and release.

A virus attaches to a specific receptor site on the host-cell membrane through attachment proteins in the capsid or proteins embedded in its envelope. The attachment is specific, and typically a virus will only attach to cells of one or a few species and only certain cell types within those species with the appropriate receptors.

CONCEPT IN ACTION

View this video for a visual explanation of how influenza attacks the body.

Unlike animal viruses, the nucleic acid of bacteriophages is injected into the host cell naked, leaving the capsid outside the cell. Plant and animal viruses can enter their cells through endocytosis, in which the cell membrane surrounds and engulfs the entire virus. Some enveloped viruses enter the cell when the viral envelope fuses directly with the cell membrane. Once inside the cell, the viral capsid is degraded and the viral nucleic acid is released, which then becomes available for replication and transcription.

The replication mechanism depends on the viral genome. DNA viruses usually use host cell proteins and enzymes to make additional DNA that is used to copy the genome or be transcribed to messenger RNA (mRNA), which is then used in protein synthesis. RNA viruses, such as the influenza virus, usually use the RNA core as a template for synthesis of viral genomic RNA and mRNA. The viral mRNA is translated into viral enzymes and capsid proteins to assemble new virions (Figure). Of course, there are exceptions to this pattern. If a host cell does not provide the enzymes necessary for viral replication, viral genes supply the information to direct synthesis of the missing proteins. Retroviruses, such as HIV, have an RNA genome that must be reverse transcribed to make DNA, which then is inserted into the host’s DNA. To convert RNA into DNA, retroviruses contain genes that encode the virus-specific enzyme reverse transcriptase that transcribes an RNA template to DNA. The fact that HIV produces some of its own enzymes, which are not found in the host, has allowed researchers to develop drugs that inhibit these enzymes. These drugs, including the reverse transcriptase inhibitor AZT, inhibit HIV replication by reducing the activity of the enzyme without affecting the host’s metabolism.

The last stage of viral replication is the release of the new virions into the host organism, where they are able to infect adjacent cells and repeat the replication cycle. Some viruses are released when the host cell dies and other viruses can leave infected cells by budding through the membrane without directly killing the cell.

ART CONNECTION

Influenza virus is packaged in a viral envelope, which fuses with the plasma membrane. This way, the virus can exit the host cell without killing it. What advantage does the virus gain by keeping the host cell alive?

PT IN ACTION

Click through this tutorial on viruses to identify structures, modes of transmission, replication, and more.

Viruses and Disease

Viruses cause a variety of diseases in animals, including humans, ranging from the common cold to potentially fatal illnesses like meningitis (Figure 17.1.6). These diseases can be treated by antiviral drugs or by vaccines, but some viruses, such as HIV, are capable of avoiding the immune response and mutating so as to become resistant to antiviral drugs.

Vaccines for Prevention

While we do have limited numbers of effective antiviral drugs, such as those used to treat HIV and influenza, the primary method of controlling viral disease is by vaccination, which is intended to prevent outbreaks by building immunity to a virus or virus family. A vaccine may be prepared using weakened live viruses, killed viruses, or molecular subunits of the virus. In general, live viruses lead to better immunity, but have the possibility of causing disease at some low frequency. Killed viral vaccine and the subunit viruses are both incapable of causing disease, but in general lead to less effective or long-lasting immunity.

Weakened live viral vaccines are designed in the laboratory to cause few symptoms in recipients while giving them immunity against future infections. Polio was one disease that represented a milestone in the use of vaccines. Mass immunization campaigns in the U.S. in the 1950s (killed vaccine) and 1960s (live vaccine) essentially eradicated the disease, which caused muscle paralysis in children and generated fear in the general population when regional epidemics occurred. The success of the polio vaccine paved the way for the routine dispensation of childhood vaccines against measles, mumps, rubella, chickenpox, and other diseases.

Live vaccines are usually made by attenuation (weakening) of the “wild-type” (disease-causing) virus by growing it in the laboratory in tissues or at temperatures different from what the virus is accustomed to in the host. For example, the virus may be grown in cells in a test tube, in bird embryos, or in live animals. The adaptation to these new cells or temperature induces mutations in the virus’ genomes, allowing them to grow better in the laboratory while inhibiting their ability to cause disease when reintroduced into the conditions found in the host. These attenuated viruses thus still cause an infection, but they do not grow very well, allowing the immune response to develop in time to prevent major disease. The danger of using live vaccines, which are usually more effective than killed vaccines, is the low but significant risk that these viruses will revert back to their disease-causing form by back mutations. Back mutations occur when the vaccine undergoes mutations in the host such that it readapts to the host and can again cause disease, which can then be spread to other humans in an epidemic. This happened as recently as 2007 in Nigeria where mutations in a polio vaccine led to an epidemic of polio in that country.

Some vaccines are in continuous development because certain viruses, such as influenza and HIV, have a high mutation rate compared to other viruses or host cells. With influenza, mutation in genes for the surface molecules helps the virus evade the protective immunity that may have been obtained in a previous influenza season, making it necessary for individuals to get vaccinated every year. Other viruses, such as those that cause the childhood diseases measles, mumps, and rubella, mutate so little that the same vaccine is used year after year.

Vaccines and Antiviral Drugs for Treatment

In some cases, vaccines can be used to treat an active viral infection. In the case of rabies, a fatal neurological disease transmitted in the saliva of rabies virus-infected animals, the progression of the disease from the time of the animal bite to the time it enters the central nervous system may be two weeks or longer. This is enough time to vaccinate an individual who suspects being bitten by a rabid animal, and the boosted immune response from the vaccination is enough to prevent the virus from entering nervous tissue. Thus, the fatal neurological consequences of the disease are averted and the individual only has to recover from the infected bite. This approach is also being used for the treatment of Ebola, one of the fastest and most deadly viruses affecting humans, though usually infecting limited populations. Ebola is also a leading cause of death in gorillas. Transmitted by bats and great apes, this virus can cause death in 70–90 percent of the infected within two weeks. Using newly developed vaccines that boost the immune response, there is hope that immune systems of affected individuals will be better able to control the virus, potentially reducing mortality rates.

Another way of treating viral infections is the use of antiviral drugs. These drugs often have limited ability to cure viral disease but have been used to control and reduce symptoms for a wide variety of viral diseases. For most viruses, these drugs inhibit the virus by blocking the actions of one or more of its proteins. It is important that the targeted proteins be encoded for by viral genes and that these molecules are not present in a healthy host cell. In this way, viral growth is inhibited without damaging the host. There are large numbers of antiviral drugs available to treat infections, some specific for a particular virus and others that can affect multiple viruses.

Antivirals have been developed to treat genital herpes (herpes simplex II) and influenza. For genital herpes, drugs such as acyclovir can reduce the number and duration of the episodes of active viral disease during which patients develop viral lesions in their skins cells. As the virus remains latent in nervous tissue of the body for life, this drug is not a cure but can make the symptoms of the disease more manageable. For influenza, drugs like Tamiflu can reduce the duration of “flu” symptoms by one or two days, but the drug does not prevent symptoms entirely. Other antiviral drugs, such as Ribavirin, have been used to treat a variety of viral infections.

By far the most successful use of antivirals has been in the treatment of the retrovirus HIV, which causes a disease that, if untreated, is usually fatal within 10–12 years after being infected. Anti-HIV drugs have been able to control viral replication to the point that individuals receiving these drugs survive for a significantly longer time than the untreated.

Anti-HIV drugs inhibit viral replication at many different phases of the HIV replicative cycle. Drugs have been developed that inhibit the fusion of the HIV viral envelope with the plasma membrane of the host cell (fusion inhibitors), the conversion of its RNA genome to double-stranded DNA (reverse transcriptase inhibitors), the integration of the viral DNA into the host genome (integrase inhibitors), and the processing of viral proteins (protease inhibitors).

When any of these drugs are used individually, the virus’ high mutation rate allows the virus to rapidly evolve resistance to the drug. The breakthrough in the treatment of HIV was the development of highly active anti-retroviral therapy (HAART), which involves a mixture of different drugs, sometimes called a drug “cocktail.” By attacking the virus at different stages of its replication cycle, it is difficult for the virus to develop resistance to multiple drugs at the same time. Still, even with the use of combination HAART therapy, there is concern that, over time, the virus will evolve resistance to this therapy. Thus, new anti-HIV drugs are constantly being developed with the hope of continuing the battle against this highly fatal virus.

Summary

Viruses are acellular entities that can usually only be seen with an electron microscope. Their genomes contain either DNA or RNA, and they replicate using the replication proteins of a host cell. Viruses are diverse, infecting archaea, bacteria, fungi, plants, and animals. Viruses consist of a nucleic-acid core surrounded by a protein capsid with or without an outer lipid envelope.

Viral replication within a living cell always produces changes in the cell, sometimes resulting in cell death and sometimes slowly killing the infected cells. There are six basic stages in the virus replication cycle: attachment, penetration, uncoating, replication, assembly, and release. A viral infection may be productive, resulting in new virions, or nonproductive, meaning the virus remains inside the cell without producing new virions.

Viruses cause a variety of diseases in humans. Many of these diseases can be prevented by the use of viral vaccines, which stimulate protective immunity against the virus without causing major disease. Viral vaccines may also be used in active viral infections, boosting the ability of the immune system to control or destroy the virus. Antiviral drugs that target enzymes and other protein products of viral genes have been developed and used with mixed success. Combinations of anti-HIV drugs have been used to effectively control the virus, extending the lifespan of infected individuals.

Art Connections

Figure 17.1.4 Which of the following statements about virus structure is true?

A. All viruses are encased in a viral membrane.
B. The capsomere is made up of small protein subunits called capsids.
C. DNA is the genetic material in all viruses.
D. Glycoproteins help the virus attach to the host cell.

Figure 17.1.4 D

Figure 17.1.5 Influenza virus is packaged in a viral envelope, which fuses with the plasma membrane. What advantage does the virus gain by keeping the host cell alive?

Figure 17.1.5 The host cell can continue to make new virus particles.

Glossary

acellular
lacking cells
apoptosis
the cell death caused by induction of a cell’s own internal mechanisms either as a natural step in the development of a multicellular organism or by other environmental factors such as signals from cells of the immune system
attenuation
the weakening of a virus during vaccine development
capsid
the protein coating of the viral core
cytopathic
causing cell damage
glycoprotein
a protein molecule with attached carbohydrate molecules
vaccine
a weakened solution of virus components, viruses, or other agents that produce an immune response
virion
an individual virus particle outside a host cell

AP Biology Question 17: Answer and Explanation

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Question: 17

5. Once a plasmid has incorporated specific genes, such as the gene coding for the antibiotic ampicillin, into its genome, the plasmid may be cloned by

  • A. inserting it into a virus to generate multiple copies
  • B. treating it with a restriction enzyme in order to cut the molecule into small pieces
  • C. inserting it into a suitable bacterium in order to produce multiple copies
  • D. running it on a gel electrophoresis in order to determine the size of the gene of interest

Correct Answer: C

Explanation:

C To make multiple copies of a plasmid (a small circular DNA), it should be inserted into a bacterium. A plasmid would not replicate if it were inserted into a virus, so eliminate (A). If a plasmid were treated with a restriction enzyme, it would be cut into smaller fragments. This would not give us cloned versions of the plasmid, so (B) is incorrect. If the plasmid were run on a gel (using gel electrophoresis), this would only tell us the size of the plasmid therefore, (D) is also incorrect.

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Structure of Adenoviruses | Microbiology

In this article we will discuss about the structure of adenoviruses (explained with diagram).

All adenovirus particles are similar particles are medium-sized, non-enveloped having 90-100 nm diameters (Fig. 17.5). The particles have icosahedral symmetry which can easily be visible in the electron microscope by negative staining. Viral particles are composed of 252 capsomers: 240 hexons forming the faces and 12 pentons at vertices of icosahedron (2-3-5 symmetry).

Each penton bears a slender fiber. The penton fibres consist of a slender shaft with a globular head. They are involved in the process of attachment of the virus particle to the host cell via the coxsackie-adenovirus receptor on the surface of the host cell.

The thin fibres protruding from each vertex of the icosahedral particle are just visible and the triangular faces of the icosahedral particle can be made out. But during preparation for electron microscopy, the fibres easily become detached.

Adenovirus gene products and their functions are given in Table 17.2. The hexons consist of a trimer of protein II with a central pore, there is no protein I. The proteins VI, VIII and IX are the minor polypeptides which are also associated with the hexon.

They are thought to be involved in stabilization and/or assembly of the particle. The pentons are more complex the base consists of a pentamer of protein III, 5 molecules of IlIa are also associated with the penton base.

The pentons have a toxin-like activity. A trimeric fibre protein extends from each of the 12 vertices (attached to the penton base proteins) and is responsible for recognition and binding to the cellular receptor. A globular domain at the end of the adenovirus fiber is responsible for recognition of the cellular receptor.

There are at least 10 proteins in the adenovirus capsid (Table 17.2). The double-stranded linear DNA is associated with two major core proteins: terminal protein (TP) and VII. Terminal protein is covalently attached to the 5′ ends of the genome strands. Protein VII (1070 copies/particle) is arginine-rich basic protein (similar to histones) which is covalently associated with the genome forming a ‘chromatin-like’ substance.

Genome structure is one of the characters used to assign viruses to groups (70-95% homology within groups, 5-20% homology between groups). Genome of adenovirus is linear, non-segmented, dsDNA of 30-38 kb size which varies from group to groups (Fig. 17.6). Although adenovirus is larger than the other viruses in Baltimore’s group, still it is a very simple virus and is heavily reliant on the host cell for survival and replication.

Theoretically, it has the capacity to encode 30-40 genes. The terminal sequences of each strand are inverted repeats therefore, the denatured single strands can form ‘panhandle’ structures (100-140 bp). A protein of 55 kD is covalently attached to the 5′ end of each strand. It is required as primers in viral replication and ensures that the ends of the virus linear genome are adequately replicated.


Results

To ensure equivalence of samples in terms of length of infection (which may have influenced viral load and genome diversity), self-reported information from patients was used. Samples were selected so that there was no significant difference in the mean-time to the onset of symptoms for the hospitalised survivor group (6.4 days) and for the hospitalised fatal group (5.9 days). In terms of sequence quality, data from the blood samples was included if the final assembled dominant EBOV genome sequence was longer than 18,800 nucleotides and without gap (N). Using both equivalence of infection and sequence read quality to filter for sample quality, the numbers of samples for comparison were 38 hospitalised survivors and 96 hospitalised fatal cases. The general statistics of these cases are summarised in Additional file 1: Table S1.

Reflecting the observations from Guinea [2], on average, the EBOV load was significantly higher in acute patients at presentation in the hospitalised fatal group compared to the hospitalised survivor group (Fig. 1a). To determine the viral genome population in an individual, reads were mapped to a reference EBOV genome to call a dominant viral genome sequence. This was used as a template in the second round of mapping to generate the reference EBOV genome for each individual patient. The variation in the four nucleotides at each site along the reference EBOV genome was counted for the individual patient. A sliding window of 200 nucleotides was used to derive and compare the average frequency in nucleotide variation along the genome.

Ebola genome-wide mutational bias and viral load. a Comparison of the viral load (1/Ct) in hospitalised fatal versus hospitalised survived blood samples taken during the acute phase upon admission to an Ebola virus treatment centre. These data followed the normal distribution, so P values were calculated with a two-sided t test. b Comparison of the nucleotide variation from the dominant genome sequence in an individual patient in hospitalised fatal versus hospitalised survived cases. The variation frequency was calculated by transversion or transition deviations using a 200-nucleotide sliding window, and the P values were calculated with a one-sided Wilcoxon rank sum test as the data did not fit a normal distribution. c Q-Q plots were used to compare the distribution of the average nucleotide deviation in an individual patient in hospitalised fatal versus hospitalised survived cases using a 200-nucleotide sliding window along the genome for hospitalised survived versus hospitalised fatal cases. d Average nucleotide variation along the Ebola genome calculated by substitutions leading to either transversion or transition changes using a 200-nucleotide sliding window. e Comparison of the viral load (1/Ct) in hospitalised fatal versus hospitalised survived cases. A two-sided Spearman rank correlation test was used to estimate the correlation of the average nucleotide variation and viral load (1/Ct) of each sample from a patient, where the R value is the correlation coefficient ranging in − 1 (strong negative correlation) and + 1 (strong positive correlation), and P is the P value for this test

The data provided information on the dominant viral genome sequence and the frequency and position of minor variants in the EBOV genome between the hospitalised survivor group and the hospitalised fatal group. These corresponded to the transition and transversion variations from the dominant viral genome sequence (Fig. 1b, c). In general, the frequency of minor variants which represented transitions was higher than the frequency of transversions. The variation in the frequency of both transition and transversion deviations was broader in the hospitalised survivor group compared to the hospitalised fatal group (Fig. 1b). To investigate the distribution of these deviations across the genome, the average frequency of the minor variants was plotted along the EBOV genome (Fig. 1d). This showed there were regions along the genome, including the L gene, that exhibited greater deviation from the dominant viral genome sequence and also that in a region of GP, transversions were more frequent than transitions in EBOV genomes from hospitalised survivors compared to hospitalised fatal cases (Additional file 1: Fig. S1).

The frequency of deviation from the dominant viral genome sequence may have been influenced by viral load, and the more genomes present, the more variation might exist. To investigate this, a Spearman rank correlation test was performed (Fig. 1e). This showed that the frequency of transition and transversion deviations from the dominant viral genome sequence was negatively related to viral load. The data implied a greater diversity in EBOV genomes in patients with lower viral loads compared to patients with high viral loads. A generalised linear model (glm) was used to investigate this observation and showed no significant difference in the slope and intercept between survivors and fatalities in any plot of Fig. 1e (Additional file 1: Table S2). This suggested, in dominant viral genome sequence present in hospitalised survivors and hospitalised fatal cases at presentation, with the same viral load, there were no differences in transitions or transversions.

The minor variant population may have resulted in non-synonymous changes that had functional divergence from the dominant viral genome sequence, resulting in differences in the primary amino acid sequence from that coded by dominant viral genome. This would lead to neutral, loss or gain in function of the affected viral protein. If the minor variant formed a significant proportion of the virus population, then any changes in viral protein function due to the minor variant may have had an overall effect on the activity of the viral protein in the infection.

To investigate this, the amino acid sequence space for all EBOV proteins was determined and the contribution of minor variants compared to the dominant viral genome sequence (Fig. 2a and Additional file 1: Fig. S2). In general, minor variants resulted in a small frequency of changes to the background protein sequence in all of the EBOV proteins (the dominant viral genome sequence by definition was still the majority sequence). However, in VP24 and L, there were several peaks where the frequency of the minor variants would have resulted in 20% or more of the protein space having a different amino acid at that position (Fig. 2a). The minor variant changes in VP24 led to one amino acid being present in the minor variants that was different from the dominant viral genome sequence but was similar for both hospitalised survivor and hospitalised fatal cases (Fig. 2a). In the L protein, three of these sites between hospitalised survivor and hospitalised fatal cases showed the highest difference with the most significant P values than all other amino acid sites of EBOV proteins: positions 572, 986 and 2061 (Fig. 2a, b Additional file 1: Fig. S2). These deviations from the dominant viral genome sequence had a strong negative correlation with viral load (for each position the R value was less than − 0.69 (range − 1 to + 1) (Fig. 2c–e). These changes were mostly transversions, except at position 986, where these were predominately transitions (Fig. 3). Also, a glm showed significant differences of slope and intercept between survivors and fatalities in the data presented in Fig. 2c–e (Additional file 1: Table S2). This suggested that the frequency of non-synonymous changes at positions 572, 986 and 2061 of the L protein under the same viral load (1/Ct value) was significantly different between hospitalised survivors and hospitalised fatalities.

Analysis of non-synonymous changes and their correlation with viral load in acute patients. a The average non-synonymous variation in codon frequency at every amino acid site of each EBOV protein. b Comparison of the non-synonymous nucleotide substitution frequency in the L protein at positions 572, 986 and 2061, and the P values were calculated with a one-sided Wilcoxon rank sum test. c A two-sided Spearman rank correlation test was used to estimate the correlation of average non-synonymous deviation in viral genomes with viral load (1/Ct) at positions 572, 986 and 2061 in patients who were either hospitalised fatal versus hospitalised survived cases, where the R value is the correlation coefficient ranging in − 1 (strong negative correlation) and 1 (strong positive correlation), and P is P value for this test

Comparison between Ts and Tv ratios that resulted in a non-synonymous change in positions 572, 986 and 2061 in the L protein and position 28 in VP24. The P values were calculated with a one-sided Wilcoxon rank sum test

The predominant amino acid changes caused by minor variants at positions 572, 986 and 2061 in the L protein are shown in Additional file 1: Fig. S3. These include N572S, Q986R and F2061S and are more frequent in the EBOV minor variant population in the hospitalised survivor group than the hospitalised fatal group (Fig. 4a). Moreover, their usage correlated with a lower viral load in patients and therefore the hospitalised survivor category (Fig. 4b). One of the deviations from the dominant genome sequence in the L protein at position 986 was for a stop codon and would have resulted in a truncated L protein. This stop codon was present in a greater frequency, although in less patients, in the hospitalised survivor versus hospitalised fatal cases (Fig. 5a, b). For example, in one hospitalised survivor, the stop protein at position 986 reached a frequency of approximately 15% in the minor variant population. Indeed, stop codons were present at low frequency in all EBOV proteins (Fig. 5a), but it appeared more frequently at position 986 in the L protein than any other position in viral proteins (Fig. 5c). Similar to the other amino acid changes caused by minor variants at positions 572, 986 and 2061, the stop codon frequency at position 986 was more frequent in hospitalised survivors than hospitalised fatal cases (Fig. 5a, b) and was also negatively related to viral load (Fig. 5d). The glm showed significant differences in slope and intercept between data from hospitalised survivor and hospitalised fatal cases in Fig. 5d (Additional file 1: Table S2). This suggested that the stop codon was present in a greater frequency at position 986 of L protein under the same viral load (1/Ct value).

a Comparison of three amino acid variation frequencies in the L protein at positions 572, 986 and 2061. P values were calculated with the one-tailed Wilcoxon rank sum test. b A Spearman rank correlation test was used to estimate the correlation of these three amino acid variation frequencies with viral load (1/Ct) at positions 572, 986 and 2061, where the R value is the correlation coefficient ranging from − 1 (strong negative correlation) to + 1 (strong positive correlation), and P is the P value for this test. In a and b, only the samples with at least amino acid variation are shown

Analysis of the frequency of stop codon substitution in viral proteins and viral load. a Comparison of stop codon frequency in the L protein at position 986. P values were calculated with the one-sided Wilcoxon rank sum test, with the average stop codon frequency at position 986 in the EBOV L protein and compassion between hospitalised fatal and hospitalised survived cases. b A Q-Q plot was used to compare the distribution of the stop codon at position 986 in the L protein between hospitalised fatal and hospitalised survived cases. The values below the line suggest the data, i.e. the presence of the stop codon, was more frequent in the hospitalised survivor cases. c The summary of stop codon frequency in all EBOV proteins compared between hospitalised fatal and hospitalised survived cases. d A two-sided Spearman rank correlation test was used to estimate the correlation of stop codon frequency with viral load (1/Ct) at position 986, where the R value is the correlation coefficient ranging from − 1 (strong negative correlation) to + 1 (strong positive correlation), and P is the P value for this test. In b, d and e, only the samples with at least one stop codon are shown. In a, c and d, only the samples with at least one stop codon are shown

We postulated that changes in the minor variant frequency and concomitant change in amino acid usage in the L protein at positions 572, 986 and 2061 would have had a negative impact on virus biology—given the correlation with reduced viral load in patients (Fig. 2c–e, Fig. 4b and Fig. 5d). The L protein of the filoviruses and the wider family of the Mononegavirales has a conserved structure with functional domains separated by hinge regions (Fig. 6a). Although the presence of a stop codon would produce a truncated protein (Fig. 6b), this may have remained biologically active as it was C-terminal of the catalytic domain for RNA synthesis [17]. Several studies have shown that individual domains of the L protein in Mononegavirales have biological activity, and exogenous sequence can be inserted into the hinge regions whilst still maintaining function [18,19,20]. Likewise, the expression of L protein within a specific range may be required for optimal viral RNA synthesis [21].

Functionality of LSTOP and L3mut in an EBOV transcription/replication plasmid-based system (mini-genome) in cell culture. a, b Schematic diagrams of the conserved domains (grey boxes), functional motifs (purple) and variable regions or hinges (discontinuous green line) in EBOV L3mut and LSTOP. This diagram is based on data for filovirus and mononegavirus models for the L protein. Conserved blocks I–III constitute a RdRp, which is closely associated with a capping domain (Cap). Block VI has methyltransferase (MTase) activity, and downstream of this is located in a small C-terminal domain (CTD). Red highlighted the amino acid position where the a three most frequently found amino acid changes in the L protein at positions 572, 98s and 2061 are located and b the truncated protein due to the stop codon in L. c EBOV mini-genome system activity at different ratios between EBOV L and LSTOP and d at equal EBOV L but different LSTOP amounts. Results are shown as the mean ± S.D. from one experiment performed in triplicate. ***P < 0.001 **P < 0.01 *P < 0.05. Western blot for luciferase (LUC), EBOV L/LSTOP and house-keeping GAPDH protein abundance in cells transfected with the mini-genome system. e EBOV mini-genome system activity in the presence of the L, no L and L3mut and at different ratios between L and L3mut. Blotting showed LUC and GAPDH abundance in cells transfected with the mini-genome system plasmids. f VP35-eGFP was used in a co-immunoprecipitation (coIP) assay to examine its interaction with EBOV LSTOP. Blotting showed the presence of eGFP and viral proteins VP35/eGFP, VP35, L and NP in the cell lysates (input (I)) and coIP fraction (eluate (E)). g Proposed model of the competition between EBOV L and LSTOP for the viral RdRp co-factor VP35 and the potential reduction in the EBOV RNA synthesis observed in patients with lower viral load (inset panel)

To investigate the activity of a truncated L protein due to the stop codon at position 986, and amino acid changes due to minor variants, we made use of a mini-genome system developed in the laboratory for Ebola virus Makona [22]. Here, viral proteins required for RNA synthesis, L, NP, VP30 and VP35, are provided in trans from helper expression plasmids. These drive the replication of the mini-genome and transcription of a luciferase reporter mRNA whose cDNA has been inserted between the 3′ and 5′ UTRs of the EBOV genome. Such systems have been shown to faithfully recapitulate viral RNA synthesis [23]. The insertion of the luciferase cDNA, and concomitant activity of the luciferase reporter protein, provides a rapid readout for functional analysis of viral proteins and variants, through substitution in the helper expression plasmids.

The activity of the truncated L protein, through the replacement of the Q at position 986 with a stop codon (referred to as LSTOP), was compared to the wild-type L protein. Here, the activity of luciferase was compared between mini-genome systems supported by the L protein expression plasmid, or where this plasmid was excluded, or a combination of both the L protein and LSTOP expression plasmids or the LSTOP expression plasmid only. All of the other support plasmids, expressing NP, VP30 and VP35, were provided as normal (Fig. 6c, Additional file 1: Fig. S4). Western blot confirmed the expression of L and LSTOP. In line with previous observations, excluding the L protein led to background observable luciferase activity compared to wild-type L protein (Fig. 6c, Additional file 1: Fig. S4). As the ratio of LSTOP to L expression plasmid was increased, there was a decreasing luciferase activity, such that with LSTOP only, the level of luciferase was not significantly different from excluding the L protein expression plasmid (Fig. 6c, Additional file 1: Fig. S4). This suggested that the LSTOP could not function as a RdRp. To investigate the potential loss of the overall function of the L protein activity, increasing amounts of the LSTOP expression plasmid were titrated in, with equivalent amounts of pUC57 added to maintain the total amount of DNA during transfection. Here, for all amounts of the LSTOP expression plasmid tested, there was a significant reduction in luciferase activity from using the L expression plasmid only (Fig. 6d, Additional file 1: Fig. S5). However, there was no significant difference in luciferase activity for all of the amounts of the LSTOP. Given that N572S, Q986R and F2061S substitution as a result of minor variants could be present in the same patient (Additional file 1: Fig. S3). To evaluate the activity of these mutations in the context of the L protein, an expression variant called L3mut was constructed where all three mutations were present. The data indicated that the activity of L3mut was significantly reduced compared to the wild-type L protein (Fig. 6e, Additional file 1: Fig. S6), including when both wild-type L protein and L3mut were expressed at the same time.

From this, we postulated that not only did these minor variant proteins have no (LSTOP) or reduced activity (L3mut), they may also have acted as a sink to sequester other viral proteins required for viral RNA synthesis away from the dominant viral genome sequence for the L protein. To test this hypothesis, the capability of LSTOP to interact with VP35, a known polymerase cofactor for the L protein, and essential for replication and transcription [24,25,26], was examined. The ability of LSTOP to associate with VP35 was compared to L protein using a co-immunoprecipitation assay. Here, VP35 had been C-terminal tagged in frame with enhanced green fluorescence protein (eGFP) (forming VP35-eGFP) to allow co-immunoprecipitation with a highly specific single-chain antibody. This approach has been used to study the interacting partners of a wide variety of viral proteins, e.g. [22, 27, 28]. Although somewhat diminished compared to wild-type VP35, VP35-eGFP, in the context of the mini-genome system, still allowed the generation of luciferase activity (data not shown), suggesting the protein was still biologically active, through its interactions with the L protein. Co-immunoprecipitation indicated that VP35-eGFP could be used to pull down either the L protein or LSTOP protein but not NP (Fig. 6f, Additional file 1: Fig. S7). Overall, the data is supportive of a model (Fig. 6g) in which the presence of LSTOP protein contributes to the reduction in viral load in patients (Fig. 6g, inset panel) possibly through both the absence of RdRp activity and the ability to act as a sink for viral proteins otherwise required for RNA synthetic activity.


Virus structure

The following three basic components are included in the virus structure. The first two are present in all types of viruses. But the last one viral envelope is present mainly in the animal virus structure.

  1. A nucleic acid genome
  2. A protein capsid that covers the genome. (Genome plus protein capsid is called the nucleocapsid).
  3. Lipid envelop (In many animal viruses)

All the intact virus is called a virion. Detail of these components is right below.

A- Viral genomes:

Although the genomes of all known cells are made up of double-stranded DNA, the genomes of viruses can be made up of single-stranded or double-stranded DNA or RNA. Viruses vary greatly in their size, ranging from approximately 5-10 kb (Papovaviridae, Parvoviridae, etc.) to even more than 100-200 kb (Herpesviridae, Poxviridae). Different structures of virus genomes are given below.

  • Double-stranded – linear or circular
  • Single strand – linear or circular
  • Other structures – gapped circles

2- RNA: double-stranded – linear

Single-stranded linear structure: These single-chain genomes can be positive-sense single-stranded RNA or negative-sense single-stranded RNA or ambisense. The positive-sense single-stranded RNA can directly serve as mRNA and encode proteins, so for these viruses, viral RNA is infectious. The negative-sense single-stranded RNA is not infectious, as it must be copied into the + sense strand before it can be translated. In an Ambisense virus, some part of genome is sense strand and some part is the antisense.

The genome of some RNA viruses is segmented, which means that a virus particle contains several different RNA molecules, like different chromosomes.

B: Protein capsid

Protein capsid is an essential component of virus structure. Viral genomes are surrounded by shells of proteins known as capsids. An interesting question is how the capsid proteins recognize viral RNA or DNA, but not cellular DNA. The answer is that there is often some kind of “packaging” signal (sequence) in the viral genome that the capsid proteins recognize. A capsid is composed of repetitive structural subunits that are arranged in one of two symmetrical structures, a helix or an icosahedron. These “subunits” may consist of a single polypeptide, in simplest cases. However, in many cases, these structural subunits (also called protomers) are made up of various polypeptides. The detail of helical and icosahedral virus structures is described below.

1) Helical capsids: The first and best example studied is the plant tobacco mosaic virus (TMV), which contains a single-stranded RNA genome and a protein coat made up of a single 17.5 kd protein. This protein is arranged in a helix around the viral RNA, with 3 nucleotides of RNA fitting into a groove in each subunit. The helical capsids can also be more complex as they involve more than one protein subunit.

A Helix can be defined by two parameters, its diameter, and pitch. This structure is very stable and can be easily disassociated and re-associated by changing the ionic strength, pH, temperature, etc. The interactions that hold these molecules together are not covalent and involve H bonds, salt bridges, hydrophobic interactions, and Vander Waals forces.

Several families of animal viruses contain helical nucleocapsids, for example, Orthomyxoviridae (influenza), Rhabdoviridae (rabies) and Paramyxoviridae (bovine respiratory syncytial virus). These are all enveloped viruses.

Different capsid types in virus structure

2) Icosahedral capsids: In these structures, the subunits are arranged in the form of a hollow, quasi-spherical structure, with the genome inside. An icosahedron is defined as consisting of 20 equilateral triangular faces arranged around the surface of a sphere. They exhibit 2-3-5 symmetry.

  • 2-fold rotational symmetry through the edges.
  • 3-fold rotational symmetry through the center of each triangular face.
  • 5-fold symmetry through the center of each corner.

These corners are also called vertices, and each icosahedron has 12.

Since proteins are not equilateral triangles, each side of an icosahedron contains more than one protein subunit. The simplest icosahedron is made using 3 identical subunits to form each face, so the minimum number of subunits is 60 (20 x 3). Remember that each of these subunits could be a single protein or, more likely, a complex of multiple polypeptides.

Many viruses have a genome too large to be packaged within an icosahedron made up of only 60 polypeptides (or even 60 subunits), making them even more complicated. But in these, the total number of subunits is always a multiple of 60.

Apparent clusters or “Lumps” are often seen on the surface of the particle, when viral nucleocapsids are viewed under the electron microscope, These are generally protein subunits grouped around an axis of symmetry and have been called “morphological units” or capsomeres”

C: Viral Envelope

In some animal viruses, the nucleocapsid is surrounded by a membrane, also called an envelope. This envelope is made up of a lipid bilayer and is made up of lipids from host cells. It also contains virus-encoded proteins, often glycoproteins that are transmembrane proteins. These viral proteins serve many purposes, such as binding to receptors in the host cell, playing a role in membrane fusion and cell entry, etc. They can also form channels on the viral membrane.

Many enveloped viruses also contain matrix proteins, which are internal proteins that bind the nucleocapsid to the envelope. They are very abundant (that is, many copies per virion) and are generally not glycosylated. Some virions also contain other non-structural proteins that are used in the viral life cycle. Examples of this are replicases, transcription factors, etc. These nonstructural proteins are present in low amounts in the virion.

Enveloped viruses are formed by budding through cell membranes, usually the plasma membrane, but sometimes an internal membrane such as ER, Golgi, or nucleus. In these cases, the assembly of viral components (genome, capsid, matrix) occurs on the inner side of the membrane, the envelope glycoproteins clump together in that region of the membrane, and the virus breaks out. This ability to bud allows the virus to leave the host cell without lysing or killing the host. Conversely, unenveloped viruses and some enveloped viruses kill the host cell to escape.


Contents

    Plasmids: They are generally circular extrachromosomal DNA molecules that replicate and are transmitted independent of chromosomal DNA. They are present in prokaryotes (bacteria and archaea) and sometimes in eukaryotic organisms such as yeast. Plasmids during their cycle carry genes from one organism to another through a process called conjugation. They also often inject genes that make bacteria resistant to antibiotics. [4][5]
      : they are a type of hybrid plasmids with bacteriophages, used to transfer and replicate DNA fragments that are inserted by means of recombinant DNA techniques. To serve as a vector, it must be able to replicate together with the DNA fragment it carries. Examples are cosmids and phagemids. [6]
      : they are transposons that move directly from one position to another in the genome using a transposase to cut and stick at another locus. [8] : they are transposons that move in the genome, being transcribed into RNA and later into DNA by reverse transcriptase. Retrotransposons are present exclusively in eukaryotes. [9] : they are exclusive transposons of mammals that move in the genome, being transcribed into DNA and then into RNA, without coding for reverse transcriptase. [7]
      : They are viral agents composed of a molecule of genetic material (DNA or RNA) and with the ability to form complex particles called virions to be able to move easily between their hosts. Viruses are present in all living things. Viral particles are manufactured by the host's replicative machinery for horizontal transfer. [12][15] : they are DNA or RNA molecules, which are encapsidated as a stowaway in the virions of certain helper viruses and which depend on these to be able to replicate. Although they are sometimes considered genetic elements of their helper viruses, they are not always found within their helper viruses. [12][16] : They are viral agents that consist of circular RNA molecules that infect and replicate in plants. [12][17] : They are viral nucleic acids integrated into the genome of a cell. They can move and replicate multiple times in the host cell without causing disease or mutation. They are considered autonomous forms of transposons. Examples are proviruses and endogenous retroviruses. [18]

    CRISPR-Cas systems in bacteria and archaea are adaptive immune systems to protect against deadly consequences from MGEs. Using comparative genomic and phylogenetic analysis, researchers found that CRISPR-Cas variants are associated with distinct types of MGEs such as transposable elements. In addition, CRISPR-Cas controls transposable elements for their propagation. [19]

    MGEs such as plasmids by a horizontal transmission are generally beneficial to an organism. The ability of transferring plasmids (sharing) is important in an evolutionary perspective. Tazzyman and Bonhoeffer found that fixation (receiving) of the transferred plasmids in a new organism is just as important as the ability to transfer them. [20] Beneficial rare and transferable plasmids have a higher fixation probability, whereas deleterious transferable genetic elements have a lower fixation probability to avoid lethality to the host organisms.

    One type of MGEs, namely the Intergrative Conjugative Elements (ICEs) are central to horizontal gene transfer shaping the genomes of prokaryotes enabling rapid acquisition of novel adaptive traits. [21] [22]

    As a representative example of ICEs, the ICEBs1 is well-characterized for its role in the global DNA damage SOS response of Bacillus subtilis [23] and also its potential link to the radiation and desiccation resistance of Bacillus pumilus SAFR-032 spores, [24] isolated from spacecraft cleanroom facilities. [25] [26] [27]

    Transposition by transposable elements is mutagenic. Thus, organisms have evolved to repress the transposition events, and failure to repress the events causes cancers in somatic cells. Cecco et al. found that during early age transcription of retrotransposable elements are minimal in mice, but in advanced age the transcription level increases. [28] This age-dependent expression level of transposable elements is reduced by calorie restriction diet.

    The consequence of mobile genetic elements can alter the transcriptional patterns, which frequently leads to genetic disorders such as immune disorders, breast cancer, multiple sclerosis, and amyotrophic lateral sclerosis. In humans, stress can lead to transactional activation of MGEs such as endogenous retroviruses, and this activation has been linked to neurodegeneration. [29]

    The total of all mobile genetic elements in a genome may be referred to as the mobilome.

    Mobile genetic elements play a critical role in the spread of virulence factors, such as exotoxins and exoenzymes, among bacteria. Strategies to combat certain bacterial infections by targeting these specific virulence factors and mobile genetic elements have been proposed. [31]


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    Molecular Virology of Human Pathogenic Viruses

    Molecular Virology of Human Pathogenic Viruses presents robust coverage of the key principles of molecular virology while emphasizing virus family structure and providing key context points for topical advances in the field. The book is organized in a logical manner to aid in student discoverability and comprehension and is based on the author’s more than 20 years of teaching experience. Each chapter will describe the viral life cycle covering the order of classification, virion and genome structure, viral proteins, life cycle, and the effect on host and an emphasis on virus-host interaction is conveyed throughout the text.

    Molecular Virology of Human Pathogenic Viruses provides essential information for students and professionals in virology, molecular biology, microbiology, infectious disease, and immunology and contains outstanding features such as study questions and recommended journal articles with perspectives at the end of each chapter to assist students with scientific inquiries and in reading primary literature.


    17.5: Viruses - Biology

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    A virus is a structure that carries its own genomic material in the form of RNA or DNA to invade and replicate inside a host cell. After a virus binds to surface receptors on the host cell, it enters and rapidly disassembles, un-coding its genetic material. In the case of DNA viruses, the viral DNA directs the host cells replication proteins to synthesize new copies of the viral genome which are then transcribed and translated into viral proteins.

    Finally, the host reassembles these viral components into progeny, allowing a single virus particle to produce 1000s more, often leading to death of the host cell.

    16.1: What are Viruses?

    Overview

    A virus is a microscopic infectious particle that consists of an RNA or DNA genome enclosed in a protein shell. It is not able to reproduce on its own: it can only make more viruses by entering a cell and using its cellular machinery. When a virus infects a host cell, it removes its protein coat and directs the host&rsquos machinery to transcribe and translate its genetic material. The hijacked cell assembles the replicated components into thousands of viral progeny, which can rupture and kill the host cell. The new viruses then go on to infect more host cells.

    Why Study Viruses?

    Viruses can infect different types of cells: bacteria, plants, and animals. Viruses that target bacteria, called bacteriophages (or phages), are very abundant. Current research focuses on phage therapy to treat multidrug-resistant bacterial infections in humans. Viruses that infect cultivated plants are also highly studied since epidemics lead to huge crop and economic losses.

    Viruses were first discovered in the 19 th century when an economically-important crop, the tobacco plant, was plagued by a mysterious disease&mdashlater identified as Tobacco mosaic virus. Animal viruses are of great importance both in veterinary research and in medical research. Moreover, viruses underlie many human diseases, ranging from the common cold, chickenpox, and herpes, to more dangerous infections like yellow fever, hepatitis, and smallpox.

    The Structure of a Virus

    Viruses come in a variety of shapes that are specialized in attacking their target cell. The two major components of all viruses are the viral genome and its protective protein coat, known as the capsid. The viral genome is made up of single or double-stranded RNA or DNA, and it encodes the proteins that make up the capsid. Together, the viral genome and the capsid are known as the nucleocapsid.

    A unique feature of many eukaryotic viruses is the presence of a phospholipid membrane, known as the envelope that surrounds the capsid. This envelope typically originates from the membranes of previously infected host cells, but can also include viral proteins (called envelope proteins) attached to it. Finally, some animal viruses have a cluster of virus-encoded proteins, the viral tegument, in the space between the envelope and capsid.

    Viral Infection

    The viral life cycle can be broken into the following five steps: attachment, entry, replication, assembly, and release. The proteins on the surface of the virus help it recognize specific host cells. Some viruses use these surface proteins to bind host cell receptors and initiate internalization by endocytosis, while envelope-coated viruses can directly fuse with the host cell membrane.

    Some bacteriophages do not enter the cell they inject their genome (and viral enzymes) into the host cell. Once inside the cell, the virus is uncoated and directs the machinery of the host cell to transcribe and translate its genome. The host cell packages the new copies of the viral genome into viral particles to make progeny. The progeny viruses may be stored in the host cell before release or continually extruded from the cell by budding off from the cell membrane. The viral infection cycle is classified as lytic or lysogenic. In the lytic cycle, the new viruses burst out of the host cell thus killing it. In the lysogenic cycle, the viral DNA is incorporated into the host genome where it lays dormant and is copied each time the host cell replicates.

    Yamauchi, Yohei, and Ari Helenius. &ldquoVirus Entry at a Glance.&rdquo J Cell Sci 126, no. 6 (March 15, 2013): 1289&ndash95. [Source]

    Lin, Derek M, Britt Koskella, and Henry C Lin. &ldquoPhage Therapy: An Alternative to Antibiotics in the Age of Multi-Drug Resistance.&rdquo World Journal of Gastrointestinal Pharmacology and Therapeutics 8, no. 3 (August 6, 2017): 162&ndash73. [Source]

    Nicaise, Valérie. &ldquoCrop Immunity against Viruses: Outcomes and Future Challenges.&rdquo Frontiers in Plant Science 5 (November 21, 2014). [Source]


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