Viral Pathogenesis Flashcards
How do we classify viruses?
By their genome (DNA or RNA), viral characteristics, diseases, target tissue, geographic location (no longer preferred), and the Baltimore system (most commonly used).
How does the Baltimore system classify viruses?
By their manner of mRNA synthesis and replication, plus physical and biochemical characteristics such as size, morphology, and type of genome.
What are the 8 steps in viral replication?
Recognition, attachment, penetration/entry, uncoating, macromolecular synthesis, assembly, budding, and release.
Which step in viral replication is only present for enveloped viruses?
Budding.
What are the functions of viral attachment proteins (VAPs)?
To identify specific host cells and bind to their receptors (recognition and attachment).
How do non-enveloped viruses enter cells?
Receptor-mediated endocytosis.
How do enveloped viruses enter cells?
Fusion of viral and cellular membranes.
How does uncoating differ between non-enveloped and enveloped viruses?
Non-enveloped viruses have their capsid removed, while enveloped viruses have their envelope removed.
Once inside a cell, where do DNA and RNA viruses each go to replicate?
DNA goes to the nucleus, RNA stays in the cytoplasm.
What is macromolecular synthesis?
Synthesis of viral mRNA and proteins.
What do viruses need for macromolecular synthesis?
Host machinery (ribosomes, tRNA, and post-translational mechanisms).
What are the 3 different mechanisms for release of virus from a cell?
Lysis, budding, and exocytosis.
Single-stranded RNA viruses (ssRNA) can be either a positive strand or negative strand. What is the main difference in how they replicate?
+RNA resembles host mRNA, so it is immediately picked up by host ribosomes to start replication. -RNA does not resemble host mRNA, so it must first create its own positive strand to act as a template for replication, using RNA-dependent RNA polymerase. This means that +RNA viruses replicate faster than -RNA viruses.
What is a key feature of retroviruses?
They can integrate into the host genome.
Why do RNA viruses have a higher rate of mutation than DNA viruses?
Because they utilize RNA-dependent RNA polymerase, which has no proof-reading mechanisms and is highly prone to error.
What are the 3 mechanisms by which viral genomes can evolve, and how are they different?
1) Random mutations - small changes in the genome.
2) Recombination - exchange of genetic sequences.
3) Reassortment - exchange of segments.
What are the possible results of viral genome evolution? (5 answers)
New viruses, quasispecies, defective genomes, changes in virulence, and pseudotype viruses.
True or False: Mutations are always beneficial for the virus.
False.
List and define the different types of mutations. (6 answers)
Lethal - virus cannot replicate.
Deletion - loss or selective removal of function.
Plaque mutants - differ from wild type.
Host range mutants - differ in target tissue or species.
Attenuated mutants - cause less severe disease.
Conditional mutants - can replicate only under certain conditions.
What is the purpose of homologous or non-homologous recombination?
To repair double-strand breaks in DNA.
What is reassortment and what types of viruses does it occur in?
Exchange of part of the genome. Occurs in all segmented viruses (Influenza, Arenaviruses, Reoviruses, and Coronaviruses). This is the major event giving rise to new pandemics.
What is gene amplification/reduction?
The process during replication where certain genes are duplicated and modified, so that advantageous mutations are retained.
What are the 3 outcomes of cytopathogenesis?
Abortive infection (permissive or non-permissive)
Lytic/productive infection
Non-lytic infection
What are the 3 different mechanisms of lytic infections?
Virus-mediated lysis, apoptosis, and immune-mediated lysis.
What are the 4 types of non-lytic infections?
Persistent, latent, recurrent, and oncogenic.
True or False: The humoral immune response is useless against viral pathogens.
False. Both the humoral and cellular immune responses are important in combating viral pathogens.
What is the main antiviral response that is responsible for the classical viral symptoms, and which cytokines are involved?
Interferon response; IFN-alpha and IFN-beta.
What are the 3 local effectors and outcomes of the antiviral state induced by the IFN response?
2’5’ oligo A synthase -> RNAse L -> degrades ssRNA.
PKR -> phosphorylates eIF2 -> inhibits protein synthesis.
Mx -> inhibits viral synthesis, sequesters viral proteins, prevents integration.
What distant tissues does the IFN response act on?
CNS, bone marrow, and lymph nodes/spleen.
What factors determine what type of disease a virus will cause? (6 answers)
Tissue tropism, permissiveness of cells for replication, portal of entry, access to target tissue, virus strain, and virulence factors
What factors determine the severity of disease a virus will cause? (9 answers)
Virus strain, cytopathic effects, immune status, immunopathology, inoculum size, prior exposure, general health and nutrition, genetics, and age.
What does a short incubation period indicate about a virus?
The primary site of infection is the target tissue, and infection of that tissue is what causes the disease symptoms.
What does a long incubation period indicate about a virus?
The virus must spread from the primary site of infection and be amplified, OR the disease symptoms are causes by immunopathology.
What is the simplest way to diagnose a virus in practice?
Patient history and symptoms.
Why would we perform a lab study on a virus? (5 answers)
To identify virus to confirm diagnosis, determine appropriate antiviral therapy, define course of disease, monitor disease epidemiologically, and educate physicians and patients
What can we look for on cytology to identify a virus? (6 answers)
Cytopathic effects, morphology, lysis, syncytia, inclusion bodies, and immunofluorescence.
What can we determine using serology?
Virus identity and strain, primary infection or reinfection, acute or chronic disease.
What is electron microscopy most useful for regarding viruses?
Detecting and identifying viruses in research labs that have characteristic morphology.
