Lecture 4 - Virus Replication Cycle Flashcards
What is a resistant cell?
No receptor and cannot be naturally infected by that virus
What is a permissive cell?
Susceptible to infection (has a suitable receptor for the virus to attach to) and the capacity to support the full virus replication cycle
What is a semi-permissive cell?
Susceptible to infection but does not support the full virus replication cycle
What is a susceptible cell?
Has a functional receptor for the virus to bind to and may or may not be able to support the full virus replication cycle
What is virus tropism?
Ability of a virus to infect a specific host or a specific type of host cell
What is the multiplicity of infection (MOI) and what does it vary between?
- Average number of infectious virus particles per cell
- Varies between cell types (cell types differ in permissiveness)
What does an MOI = 1 indicate?
Using a Poisson random distribution curve, MOI=1 indicates that 1/3 of cells will receive one hit (1 virus), 1/3 of cells will receive more than one hit (>1 virus) and 1/3 of cells will receive less than one hit. This means that about 33% of cells will not get infected at this MOI
What MOI is required for complete, synchronous infection of the cell monolayer (>99% of cells get infected)
MOI > 5
What is the procedure for obtaining a virus growth curve
- Using MOI = 5-10, apply viruses at 4 degrees C (allows for attachment but not entry to synchronise infection)
- Change temperature to 37 degress
- Harvest extracellular supernatant and virus-infected cells at specific time points over hours or days and titre virus in each fraction
- Compare and contrast eclipse and latent phase for enveloped and naked viruses
What 2 things are required for virus attachment to a host cell?
Viral-attachment protein (VAP) and a specific cell receptor
What occurs during virus penetration?
The virus crosses a cell or endosomal membrane
What is the difference in uncoating location for RNA and DNA viruses
RNA viruses uncoat in the cytoplasm
DNA viruses uncoat in the nucleus
What 2 ESSENTIAL steps need to occur for successful virus uncoating?
- The stable virus capsid structure needs to be destabilized (metastability)
- Uncoating needs to deliver the virus genome in a replication-competent format to the correct subcellular compartment
What is required for a genome to be in a replication competent format?
Nucleic acid plus any essential proteins
What is the correct subcellular compartment an RNA virus genome needs to be delivered to?
Cytoplasm
What is the correct subcellular compartment a DNA virus genome need to be delivered to?
Nucleus
What 2 types of release from the host cell may occur for viruses?
Budding or lysis
What are the 3 steps in virus entry and what is the function of entry?
Attachment, penetration and uncoating
Delivery of replication competent form of genome to the correct subcellular compartment
What are the 3 steps of viral macromolecular synthesis?
Transcription, translation and genome replication
Does viral MMS occur simultaneously or in discrete steps?
Simultaneously
What are 2 types of control for viral MMS?
Cis factors and trans factors
What are the 2 steps in virus maturation?
assembly and release
What property of viruses are entry and maturation dependent on?
Whether the virus is naked or enveloped
What is an abortive virus cell infection and what causes it? What permissiveness would these cells have?
No infectious virus progeny are produced because the virus replication cycle is stalled before maturation
Often due to lack of host cell factor required for virus replication
Semi-permissive cells
What is a productive virus cell infection and what does it look like?
Production and release of infectious progeny virions
Often CPE are observed
What is a latent virus cell infection?
Persistence of viral genome in host cells with no detectable virus production, often subject to reactivation
What is a persistent virus cell infection? Is it lytic or non-lytic? Would you expect to observe cytopathic effects in a persistent infection?
Productive, long-term infection generating infectious progeny virions.
Non-lytic infection
Frequently CPE are absent
What is a transforming virus cell infection and what can it cause? What is the permissivity of these cells?
Little or no virus production, altered cell growth and morphology that may lead to cancer.
What are the characteristics of an acute viral infection?
Usually rapid and self-limiting (or cleared by host response) but can be fatal
What is an oncogenic virus?
Viruses that induce cell transfomation and cancer
What are 3 examples of intrinsic host defenses to viruses and what they do
- Autophagy disrupts intracellular virus replication
- Apoptosis kills virally infected cells
- microRNAs inhibit virus replication
What are 3 examples of innate host defense mechanisms?
- Complement
- Natural killer cells
- Antigen presenting cells
What are 3 ways host cells can sensethe presence of a virus?
- virus binding and activation of host cell receptors
- activation of nucleic acid receptors on endosomes (TLR)
- nucleic acid-binding proteins in the cytoplasm (RIG-1, PKR)
What is the result of activating virus-sensor pathways?
Lead to production and release of soluble immune mediators (cytokines, chemokines) which recruit and activate specific adaptive immune responses