Chapter 6: Viruses and Prions
General Virus Characteristics
Viruses are submicroscopic, infectious agents.
Virology is the study of viruses.
Over mammal-infecting viral species have been described, with approximately infecting humans.
An estimated mammalian viruses remain uncharacterized.
Approximately of viruses that infect humans are harbored in other animals.
Viruses are:
Extremely small, ranging from in diameter.
Acellular, meaning they are not composed of cells.
Obligate intracellular pathogens, meaning they must infect a host cell to replicate.
Comparison of Viruses, Prokaryotes, and Eukaryotes (Table 6.1)
Cells?
Viruses: No
Prokaryotes: Yes
Eukaryotes: Yes
Considered alive?
Viruses: No
Prokaryotes: Yes
Eukaryotes: Yes
Relative size
Viruses: Generally smaller than prokaryotes; most require electron microscopy to be seen.
Prokaryotes: Mostly bigger than viruses and smaller than eukaryotes; usually seen with light microscopy.
Eukaryotes: Usually bigger than prokaryotes and viruses; often visible with light microscopy.
Filterable?
Viruses: Yes
Prokaryotes: No (with exceptions for some very small filterable bacteria)
Eukaryotes: No
Structure
Viruses: Protein capsid coating and nucleic acid.
Prokaryotes: Cells without nuclei or other membrane-bound organelles.
Eukaryotes: Cells with nuclei and membrane-bound organelles.
Replication
Viruses: Host cell energy and machinery are hijacked to replicate the virus.
Prokaryotes: Binary fission (asexual).
Eukaryotes:
Mitosis (asexual)
Meiosis (sexual)
Exhibit metabolism?
Viruses: No
Prokaryotes: Yes
Eukaryotes: Yes
Genome composition
Viruses: DNA or RNA
Prokaryotes: DNA
Eukaryotes: DNA
Diverse Structural and Genomic Features
Viruses can infect every branch in the tree of life.
Focus is on:
Bacteriophages: viruses that infect bacteria.
Animal viruses: viruses that infect animals and humans.
A virion refers to a single, infectious virus particle.
They possess an exterior protective protein capsid.
They contain genetic material, which can be either DNA or RNA.
Viral Capsids
Capsid: A protein shell that packages and protects the viral genome.
It accounts for the bulk of a virion's mass.
Made of repeating capsomere subunits.
Most animal viruses have either helical or icosahedral capsids.
Helical capsids appear as hollow tubes.
Icosahedral capsids resemble three-dimensional polygons.
Deviations from these two basic structures are classified as complex capsids.
Bacteriophages typically exhibit a complex capsid structure.
They often have capsids with icosahedral symmetry.
Their capsids are frequently associated with additional complex structures (e.g., sheath, baseplate, tail fiber, pin) that facilitate the injection of their genome into target cells.
Viral Envelopes
Enveloped viruses possess a lipid-based envelope surrounding the capsid.
This envelope arises from the virus budding off the host cell, taking a portion of the cell membrane with it.
Naked (or nonenveloped) viruses lack an envelope.
They are released from the host cell by lysing (bursting) it.
Animal viruses can be either enveloped or naked.
Bacteriophages always lyse host cells for release, therefore they are always naked.
Viral Spikes (Peplomers)
Many viruses have spikes (also known as peplomers) that may protrude from the viral capsid or envelope.
These are glycoprotein extensions that aid viruses in attaching to and gaining entry into host cells.
Influenza viruses frequently mutate, leading to small changes in their spike proteins.
Influenza A spikes include: Hemagglutinin (HA) and Neuraminidase (NA).
Viral Genomes
Most viruses have fewer than genes.
Viral genes primarily encode:
Capsomere proteins.
Enzymes necessary for viral replication.
Structural factors.
Viral genomes exhibit diverse compositions and arrangements:
Can be either RNA or DNA.
Can be single-stranded (ss) or double-stranded (ds).
Can exist as a single section or in segmented sections.
Can have a circular or linear arrangement.
Specifically:
DNA viral genomes are typically circular or linear, often double-stranded, but can also be single-stranded.
RNA viral genomes are usually linear or segmented, often single-stranded, but can also be double-stranded.
The fundamental goal of all viruses is to compel a host cell to produce viral proteins, enabling the construction of new virions.
Making mRNA from Viral Genomes
Viruses employ varied strategies to synthesize mRNA that the host cell's ribosomes can translate into proteins.
Double-stranded DNA (dsDNA) viruses: The viral DNA is transcribed into mRNA using host RNA polymerases, and this mRNA is then translated into protein.
Single-stranded DNA (ssDNA) viruses: The ssDNA genome is first converted into a double-stranded form before transcription can occur.
Single-stranded positive RNA (ssRNA+) viruses: The ssRNA genome itself functions directly as an mRNA and is immediately translated by host cell ribosomes.
Single-stranded negative RNA (ssRNA-) viruses: The RNA genome is complementary to mRNA. It must be transcribed into mRNA by viral RNA-dependent RNA polymerases (RdRPs), as host cells lack this enzyme.
Single-stranded retroviruses: These RNA viruses have a positive-sense RNA genome but use a unique pathway. Their RNA genome is converted into DNA by a viral enzyme called reverse transcriptase. This DNA is typically integrated into the host cell's DNA (forming a provirus), and then transcribed into mRNA by host enzymes.
Double-stranded RNA (dsRNA) viruses: The dsRNA genome is transcribed to make mRNA, a process that also requires viral RNA-dependent RNA polymerases.
Viral Genome Evolution
Viruses exhibit a faster rate of genomic change compared to living infectious agents due to several factors:
Quick replication time.
Production of a large quantity of virions.
RNA genomes mutate more frequently than DNA genomes because DNA polymerases possess proofreading capabilities, which minimize errors, whereas RNA polymerases lack proofreading functions, leading to more mutations.
Mutations can have neutral, beneficial, or deleterious effects on the virus.
Genetic changes that limit infectivity lead to attenuated strains, which are often utilized in vaccines.
Beneficial mutations may enable the virus to:
Escape detection by the host immune system.
Broaden its host range (infect more species).
Expand its tropism (infect a wider range of tissues or cells).
Increase its infectivity.
Reassortment is a significant genetic event that can occur when two different viral strains co-infect a single host cell. This leads to the emergence of new viral strains with altered genetic makeup.
Antigenic Drift and Antigenic Shift (Specific to Influenza Viruses)
Following infection (or vaccination) with influenza, the host immune system recognizes the virion's HA (Hemagglutinin) and NA (Neuraminidase) spikes.
These spikes serve as antigens against which the immune system produces specific antibodies.
Antigenic drift: Influenza's RNA genome frequently mutates, causing minor, gradual changes to the HA and NA spikes. These small changes necessitate annual updates to influenza vaccines.
Antigenic shift: Occasionally, influenza viruses undergo a major genetic reassortment, particularly when a host cell is co-infected by two different influenza strains. This results in entirely new HA and/or NA spike combinations.
Antigenic shift can lead to:
Increased infectivity.
Expanded host range.
A loss of residual immune protection in people from previous infections or vaccinations.
It can potentially set the stage for a pandemic due to the lack of widespread immunity against the new strain.
Classifying and Naming Viruses
The International Committee on Taxonomy of Viruses (ICTV) is responsible for developing criteria for naming and refining naming conventions for viruses.
Viruses are classified based on the following properties:
Type of nucleic acid present (DNA or RNA).
Capsid symmetry (helical, icosahedral, or complex).
Presence or absence of an envelope.
Genome architecture (e.g., ssDNA, dsDNA, ssRNA+, ssRNA-, dsRNA).
Medically Important DNA and RNA Virus Families (Examples)
DNA Viruses:
Parvoviridae: ssDNA, naked, icosahedral (e.g., Human parvovirus B19 causing fifth disease).
Papillomaviridae: dsDNA circular, naked, icosahedral (e.g., Human papilloma viruses causing warts, some strains cause cervical cancer).
Adenoviridae: dsDNA linear, naked, icosahedral (e.g., Adenoviruses causing certain colds).
Hepadnaviridae: dsDNA circular, enveloped, icosahedral (e.g., Hepatitis B virus).
Herpesviridae: dsDNA linear, enveloped, icosahedral (e.g., Herpes simplex viruses causing oral and genital herpes; Varicella-zoster virus causing chickenpox).
Poxviridae: dsDNA linear, enveloped, complex (e.g., Smallpox virus).
RNA Viruses:
Reoviridae: dsRNA segmented, naked, icosahedral (e.g., Rotavirus causing diarrhea).
Calciviridae: ssRNA+ nonsegmented, naked, icosahedral (e.g., Hepatitis E virus, Norovirus causing gastroenteritis).
Picornaviridae: ssRNA+ nonsegmented, naked, icosahedral (e.g., Poliovirus, Hepatitis A virus, Rhinoviruses causing colds).
Flaviviridae: ssRNA+ nonsegmented, enveloped, icosahedral (e.g., Hepatitis C virus, West Nile virus, Dengue fever virus).
Togaviridae: ssRNA+ nonsegmented, enveloped, icosahedral (e.g., Rubella virus).
Retroviridae: ssRNA+ nonsegmented, has reverse transcriptase, enveloped, icosahedral (e.g., HIV causing AIDS; Human T-lymphotropic virus causing leukemia).
Coronaviridae: ssRNA+ nonsegmented, enveloped, helical (e.g., SARS virus, common cold viruses).
Paramyxoviridae: ssRNA- nonsegmented, enveloped, helical (e.g., Measles virus, Mumps virus).
Filoviridae: ssRNA- nonsegmented, enveloped, helical (e.g., Ebola virus).
Rhabdoviridae: ssRNA- nonsegmented, enveloped, helical (e.g., Rabies virus).
Bunyaviridae: ssRNA- segmented, enveloped, helical (e.g., Hanta virus causing hemorrhagic fever).
Orthomyxoviridae: ssRNA- segmented, enveloped, helical (e.g., Influenza viruses).
Arenaviridae: ssRNA- segmented, enveloped, helical (e.g., Lassa fever virus).
Host Range and Tropism
Host range: Refers to the collection of different species that a virus is capable of infecting.
Some viruses are species-specific (e.g., Measles virus only infects humans), while others can infect multiple species.
Tropism: Refers to the specific tissues or cell types that a virus can infect.
This specificity is primarily due to interactions between viral surface factors and host cell receptors.
Viruses can exhibit a broad tropism (infecting a wide range of host cells or tissues) or a narrow tropism (infecting only one type of host cell or tissue).
Virus Sizes
Viruses display a wide range of sizes that require specialized microscopy:
Rhinoviruses and polioviruses are as small as in diameter.
Ebola and pandoraviruses have lengths nearing .
Pithovirus, discovered in , is one of the largest viruses, with a length of .
For comparison:
Bacteriophage T4 is .
HIV is .
An E. coli bacterium is approximately long.
A human red blood cell has a diameter of .
Standardized Naming Rules for Viruses
Unlike cellular organisms, viruses are not assigned to domains, kingdoms, phyla, or classes.
The order level is the highest taxonomic rank for viruses.
Viral taxonomy follows a hierarchical structure under the order level:
Order: Italicized, first letter capitalized, always ends in "virales" (e.g., Herpesvirales).
Family: Italicized, first letter capitalized, always ends in "viridae" (e.g., Herpesviridae).
Subfamily: Italicized, first letter capitalized, always ends in "virinae" (e.g., Alphaherpesvirinae).
Genus: Italicized, first letter capitalized, always ends in "virus" (e.g., Simplexvirus).
Species: Italicized, first word capitalized, proper nouns capitalized; should not be abbreviated (e.g., Human herpesvirus-1, also known as Herpes simplex virus-1).
Common name: Often the same as the species name but not italicized, only proper nouns are capitalized; may be abbreviated after initial full use (e.g., human herpes virus-1 (HHV-1), also known as herpes simplex virus-1 (HSV-1)).
Introduction to Viral Replication Pathways
Once inside a host cell, a virus commandeers the host cell's energy, enzymes, organelles, and molecular building blocks to synthesize new virions.
Generalized Bacteriophage Replication
Lytic Replication Pathway: This pathway leads to the immediate production of new virions and the subsequent death of the host bacterial cell as newly made bacteriophages are released.
Attachment (Adsorption): The phage binds specifically to the bacterial cell surface.
Penetration (Entry): The phage injects its genetic material (genome) into the host cell; the empty capsid typically remains outside.
Replication (Synthesis): The phage commandeers host cell factors to transcribe and translate viral genes. The viral genome is replicated, and host cell DNA is often broken down by bacteriophage DNAases.
Assembly (Maturation): The newly replicated genome is packed into capsids, and phage structures are assembled.
Release: The bacterial cell lyses (bursts), releasing the newly formed phages.
Lysogenic Replication Pathway (carried out by temperate phages): Involves an initial attachment and penetration, but does not immediately lead to host cell lysis.
Attachment and Penetration occur as in the lytic cycle.
Integration: The phage genome is incorporated into the host cell's chromosome, forming a prophage.
Cell Division: As the host cell divides, it copies the prophage along with its own genome, meaning all daughter cells inherit the phage genome.
Lytic Cycle Entry: If the host cell experiences stress (e.g., nutrient deprivation, UV radiation), the prophage may excise itself from the host genome and enter the lytic replication pathway.
Phage Conversion: Prophages integrated into bacterial genomes can confer new pathogenic properties to bacterial cells.
They can provide new pathogenicity factors, such as toxins.
Examples include Corynebacterium diphtheriae (diphtheria toxin) and Clostridium botulinum (botulinum toxin), both of which become pathogenic due to phage conversion.
Generalized Animal Virus Replication
Animal virus replication typically involves six general steps:
Attachment: Viral surface proteins interact with specific proteins on the host plasma membrane.
Naked viruses attach through their capsid proteins.
Enveloped viruses typically attach via their spike proteins.
Penetration (Entry): The virus enters the host cell.
Enveloped viruses can enter through endocytosis (taken in by the cell in a vesicle) or membrane fusion (the viral envelope merges with the host cell membrane, releasing the capsid and genome into the cytoplasm).
Naked viruses primarily enter by endocytosis.
Uncoating: The viral genome is released from the capsid, which is digested by enzymes within an endocytic vesicle, the cytoplasm, or the nucleus.
Replication (Synthesis): The viral genome is replicated, and viral proteins are synthesized using host cell machinery and often viral enzymes.
Assembly: New virions are constructed from the replicated genomes and synthesized viral proteins.
Release: New virions exit the host cell.
Enveloped viruses are typically released by budding, acquiring their envelope from part of the host cell membrane as they exit.
Naked viruses typically cause the host cell to rupture (lyse) during release.
Persistent Infections in Animal Viruses
Acute infections: Involve viruses infecting a host cell, producing new virions, and typically being cleared by the immune system relatively quickly.
Persistent infections: These occur when viruses employ replication strategies that allow them to evade or overcome immune system clearance, leading to long-term presence in the host. They can be either chronic or latent.
Chronic infections are characterized by:
The continuous release of virions over extended periods (e.g., months or years).
A slow progression of the disease.
A prime example is Human Immunodeficiency Virus (HIV) infection.
In HIV, the viral genome is integrated into the host cell's DNA, forming a provirus, which contributes to its chronicity and ability to evade the immune system.
Latent infections are distinguished by intermittent periods of dormancy (latency) interspersed with flare-ups.
During a flare-up, virions are shed, and the infected person experiences symptoms.
Flare-ups can be triggered by various stress factors, such as fever, sunburn, or changes in hormone levels.
Members of the Herpesviridae family are notorious for causing latent infections:
Human herpes virus-1 (HSV-1) causes cold sores.
Human herpes virus-2 (HSV-2) causes genital herpes.
Varicella-zoster virus (HHV-3) causes chickenpox as the primary infection and shingles as a reactivation of the latent virus.
Persistent Infections That Can Lead to Cancer (Oncogenic Viruses)
Oncogenic viruses (oncoviruses) are viruses that have the capability to cause cancer.
They are estimated to be responsible for approximately of all human cancers.
Oncogenic viruses cause cancer by stimulating uncontrolled host cell division and/or by decreasing the host cell's responsiveness to normal death signals (apoptosis).
Examples of oncogenic viruses include:
Human papilloma viruses (HPVs): Certain strains are responsible for cervical cancer and other anogenital cancers.
Human T-lymphotropic viruses (HTLV): Associated with types of leukemia.
Clinical Aspects of Viruses and Prions
Growing Viruses in the Laboratory
Growing viruses in a laboratory setting is essential for developing vaccines and antiviral drugs.
Viruses are obligate intracellular pathogens and therefore require a host cell for replication.
Growing Bacteriophages:
Bacteriophages can be grown with relative ease in bacterial cultures.
The plaque assay is a common method: Bacteria are grown on a petri plate, phages infect and lyse the cells, leading to clear zones called plaques where host cells have been killed by the viruses.
In theory, each plaque originates from a single bacteriophage in the initial sample.
Plaque-forming units (PFUs) represent the quantity of bacteriophages in an initial sample volume.
Viral titer is the quantity of virus present in a given volume of sample.
Growing Animal Viruses:
Animal viruses are generally more difficult to cultivate than bacteriophages.
Most animal viruses are grown using tissue culture techniques (cell cultures).
Some viruses require live animal hosts (e.g., mice, rats, guinea pigs) for their growth.
Embryonated eggs (fertilized eggs) are also a useful medium for growing certain viruses, particularly for vaccine production.
Diagnostic Tests for Viruses
Accurate diagnostics are crucial for ensuring safe, virus-free transplant tissues, pharmaceutical products, and for clinical samples (e.g., tissue, blood, saliva).
Since viruses are not viewable via standard light microscopy, most detection techniques rely on molecular methods.
Clinically useful diagnostic tests must be:
Specific: The test should only detect the virus(es) of interest, avoiding false positives.
Sensitive: The test must be able to detect very low levels of the target virus, preventing false negatives.
Have short turnaround times to facilitate rapid diagnosis and treatment.
Detecting Viral Proteins
Some virus detection methods involve searching for viral proteins (antigens) in a sample.
These methods utilize purified antibodies that specifically bind to the target viral antigens.
Agglutination tests:
In one format, purified antibodies are linked to tiny latex beads. When mixed with a sample containing viral antigen, the antibodies bind the antigen, causing the beads to agglutinate (clump together).
Alternatively, viral antigens can be linked to latex beads. When mixed with a patient's sample, if patient antibodies against the virus are present, they will bind the antigens, causing the beads to agglutinate.
Enzyme-linked immunosorbent assays (ELISAs):
ELISA can be adapted to detect either viral antigens or host antibodies against viruses in a sample.
The target (antigen or antibody) adheres to a solid surface.
A change of color, often mediated by an enzyme-linked secondary antibody, indicates successful binding and the presence of the target.
Limitations of ELISA and agglutination assays:
The sample being tested must be a liquid.
Antigens must be fairly well characterized for specific antibody binding.
Antigenic shift in viruses can render them no longer detectable by tests designed for older strains.
It takes time for the host immune system to build up detectable levels of antibodies (seroconversion), meaning these tests may miss early infections.
Therefore, a combination of detection methods is often recommended for comprehensive diagnosis.
Detecting Viral Genetic Material
Detecting viral nucleic acids (DNA or RNA) is a growing and increasingly preferred trend in diagnostics due to its high sensitivity and rapidity.
The general procedure involves:
A clinical sample (e.g., sputum, blood, cerebrospinal fluid (CSF)) is collected from the patient.
Viral DNA and RNA are then extracted from the sample.
Very specific segments of the viral nucleic acid are detected by various methods:
Fluorescent-labeled probes that bind to complementary viral sequences.
Sequencing of the viral genome or specific genes.
Polymerase chain reaction (PCR), which amplifies specific viral DNA or RNA segments to detectable levels (Reverse Transcriptase PCR for RNA viruses).
Antiviral Drugs
Any step in the viral replication pathway is a potential target for antiviral drugs.
In most cases, antiviral drugs primarily limit infections rather than provide a complete cure.
Designing effective antiviral drugs presents special difficulties:
Viruses are obligate intracellular pathogens, meaning they replicate inside host cells, making it challenging to target viral processes without harming host cells.
Antivirals must be selectively toxic, meaning they should harm the virus without causing significant damage to the host.
Viruses generally have fewer chemically distinct targets compared to living pathogens (bacteria, fungi), limiting drug development options.
Due to these challenges, there are relatively few truly effective antiviral agents.
Therefore, prevention of serious viral diseases through vaccination is incredibly important.
Vaccines train the immune system to recognize viruses and are an effective means to limit infection incidence and severity.
Drugs that Block Viral Attachment, Penetration, and Uncoating
A number of antiviral drugs are designed to prevent viral entry into cells by blocking attachment or penetration.
Postexposure prophylaxis: Consists of laboratory-prepared mixtures of injectable antibodies that physically prevent viruses from binding and entering host cells.
This approach is used shortly after suspected exposure.
Examples include treatments for rabies and HIV exposure.
Docosanol: This drug blocks viral entry into host cells.
It is used topically to treat cold sores caused by Human Herpes Virus-1 (HHV-1).
Palivizumab: An injectable antibody preparation.
It specifically blocks the fusion of the respiratory syncytial virus (RSV) with host cells, preventing its entry.
Drugs that Target Viral Replication, Assembly, and Release
Nucleoside analogs: These drugs block viral replication.
There are at least a dozen drugs in this class.
They are activated into compounds that mimic normal nucleotides (adenine, guanine, cytosine, thymine, and uracil).
When incorporated into a growing viral nucleic acid chain, they act as a chemical dead end for replication, halting the synthesis process.
Examples:
Acyclovir: Inhibits viral DNA replication.
It is effective against HHV-1, HHV-2, and varicella-zoster virus.
Ribavirin: Targets viral RNA polymerases.
It is effective against respiratory syncytial virus and hepatitis C virus.
Nucleoside reverse transcriptase inhibitors (NRTIs): These drugs specifically target the reverse transcriptase enzyme found in retroviruses (like HIV).
Azidothymidine (AZT) is a well-known NRTI.
Antisense antivirals: These are short sequences of nucleotides that are complementary to specific viral RNA sequences.
They bind to viral RNA, inhibiting its translation into proteins.
The targeted RNA is subsequently destroyed by cellular enzymes.
An example is Vitravene.
Interferons: These are naturally occurring substances released by cells in response to viral infections.
They signal the presence of a virus to neighboring, uninfected cells.
Uninfected cells then make defensive changes that limit viral entry and replication.
Interferons can be produced in the laboratory and administered therapeutically to help limit the progression of certain viral infections (e.g., Hepatitis C).
Oseltamivir (Tamiflu) and Zanamivir (Relenza): These drugs are neuraminidase inhibitors.
They prevent influenza A and influenza B virions from budding off the host cell surface, thus preventing their release and spread.
Prions are Infectious Proteins
Prions are unique infectious agents comprised solely of abnormal, misfolded proteins; they contain no genetic material (DNA or RNA).
They do not replicate in the traditional sense but rather induce existing normal proteins in the host to misfold into more prion proteins through a chain reaction.
Prions cause a group of progressive neurodegenerative disorders known as Transmissible Spongiform Encephalopathies (TSEs).
Forms of spongiform encephalopathies in humans include:
Gerstmann-Sträussler-Scheinker syndrome (GSS).
Creutzfeldt-Jakob disease (CJD).
Prion diseases lead to characteristic sponge-like holes in brain tissue, resulting in severe neurological dysfunction.
Think Clinically: The Case of the Cancerous Kiss
Summary of the Case
During the 1970s, donated blood was screened only for hepatitis B virus.
A female patient named Jimena received a blood transfusion in during her third trimester of pregnancy.
Jimena gave birth to a healthy boy, Jose.
Years later, researchers discovered a previously undetected virus in Jimena's archived blood samples.
Current blood samples were collected from Jimena, but samples from her son, Jose, could not be collected because he had died.
Jose died of liver cancer.
Clinical Questions and Considerations
How could old samples of donated blood be screened to search for new viruses?
Modern molecular detection methods like PCR, sequencing, and advanced immunoassay techniques could be applied to retrospectively screen archived samples (e.g., using stored serum or plasma).
What information would be needed about this new virus in order to classify it, and how could researchers get that information?
To classify it, researchers would need:
Type of nucleic acid (DNA or RNA, single or double-stranded, linear/circular/segmented): Achieved through nucleic acid extraction and sequencing.
Capsid symmetry (helical, icosahedral, complex): Determined via electron microscopy.
Presence/absence of an envelope: Determined by electron microscopy and sensitivity to lipid solvents.
Genome architecture/sequencing: Provides gene content, replication strategies, and evolutionary relationships.
Host range and tropism: Through experimental infections in cell cultures or animal models.
How could the researchers isolate and grow a particular virus from Jimena’s blood?
Since it's an animal virus, they would likely use:
Tissue culture techniques: Inoculating various cell lines with Jimena's blood sample to find a susceptible host cell line.
Potentially, live animal hosts (if cell cultures fail) or embryonated eggs for initial isolation and propagation.
Then purification techniques like ultracentrifugation.
Assume the doctors determined the virus had an RNA genome. What kinds of antivirals would likely be prescribed to treat her infection? How would the drugs possibly work?
For an RNA virus, possible antivirals could include:
Ribavirin: Targets viral RNA polymerases.
Interferons: Stimulate host antiviral defenses.
Antisense antivirals: Block viral RNA translation.
If it's an RNA retrovirus, Nucleoside Reverse Transcriptase Inhibitors (NRTIs): Block reverse transcriptase from converting RNA to DNA.
The drugs would work by interfering with specific steps of the RNA virus replication cycle, such as RNA synthesis, protein translation, or virion assembly/release.
A small number of genes in the unnamed virus appear similar to hepatitis C virus. When doctors expose animals that had been injected with a hepatitis C vaccine to the unnamed virus, their blood shows a strong immune reaction to the unnamed virus (using a latex agglutination test). The blood of unvaccinated animals shows no reaction to the same test. What does this suggest about the shared genes?
This suggests that the shared genes encode for antigenically similar proteins (likely surface proteins or capsid components) that are recognized by antibodies generated by the hepatitis C vaccine. The immune system, having been primed against these shared antigens, mounts a cross-reactive response to the unnamed virus.
The researchers discover the new virus in six other people who had received transfusions around the same time as Jimena. The doctors monitored all of the patients over a period of years. They find that viral titers remained very low in all, with only a small increase in only a few patients. What does this suggest about the infection?
This suggests that the infection is likely a chronic persistent infection.
The low, stable viral titers over years are characteristic of chronic infections where the virus is continuously produced but often kept in check by the immune system without complete clearance.
The small increases observed in some patients might indicate mild flare-ups or periods of reduced immune control.
Besides Jose, no one suspected to be infected with the unnamed virus has died of cancer. Does this information rule out the possibility that this is an oncogenic virus? Why or why not?
No, this information does not rule out the possibility that it is an oncogenic virus.
Oncogenic viruses typically cause cancer years or even decades after initial infection.
Cancer development is a complex, multifactorial process; not every infected individual will develop cancer, and the timing can vary widely based on host genetics, co-factors, and viral load.
Jose's death from liver cancer, in the context of persistent infection, strongly suggests the virus could be oncogenic, even if others haven't developed cancer yet or may never develop it.