Viral Pathogenesis Flashcards
Define virulence. List 4 factors it is related to/determined by.
- the capacity of a virus to cause disease
- related to virus strain, dose or inoculum of the virus, inoculation route, and host factors
Viral infections are often __________. Symptomatic infection are preceded by an _______________. Symptoms are very often linked to the __________.
- asymptomatic
- incubation period
- immune response
4 different patterns of virus infection in people
- acute (common)
- chronic
- Latent, relapsing
- transforming infection
Define a transforming infection.
-where the virus immortalizes the cell, giving rise to cancer
Characteristics of acute, in vivo infections
- acute, self-limited, virus cleared by immune response
- may be symptomatic, but MORE OFTEN asymptomatic
- rapid production of virus
- rapid resolution and clearing of infection
- well suited for rapid spread: by the time patient is symptomatic, virus has already spread to new host
- modify innate immune responses
Do DNA or RNA viruses often cause acute infections?
-RNA
Viruses that cause acute infections may modify ___________ and rarely so will modify _________.
- innate immune responses
- rarely adaptive immune response
Viruses that cause acute infections often shutoff _________. Why?
- host cell protein synthesis
- to make as much virus as possible; cell becomes a virus production factory, making nothing but virus
How do Poliovirus and influenza shutoff host cell protein synthesis yet keep theirs on?
- Polio: cleaves cellular EF4, preventing host mRNA translation. However, it have secondary structures in its RNA that support ribosome binding so that only viral proteins are produced
- Influenza: “steals” 5’ caps from cellular mRNAs so they cannot be translated. It then uses the caps for viral mRNA and again, only viral proteins are produced
Viruses that cause acute infections shutoff host cell protein synthesis and are often _________. Explain.
- cytopathic
- they replicate quickly, killing the cell and producing new virions; cells experience morphological changes as result of infection
Give 4 examples of cytopathic effects observed due to an acute infection.
- inclusions: sites within cells that are packed with viral proteins; “viral factories”
- syncytia: multigiant nucleated cells
- cell swelling
- cell death from apoptosis
Some cytopathic viruses induce cell fusion (syncytia). Give 3 steps to describe how this happens.
- virus infects cell
- viral fusion protein delivered to surface
- infected cell fuses with adjoining cell
surface proteins help virus fuse with cell, but also help infected cell fuse with uninfected cell
What branch of the immune system do viruses causing acute infections have to deal with?
- innate immunity
- adaptive would protect you from subsequent infections, but not help with the initial; this is the job of the innate immunity
_________ is the hallmark of the innate response to virus infection. Which type are particularly important.
- interferon release
- Type I interferons like IFN-alpha and beta
Describe IFN production
- there is one IFN-B and many IFN-a genes
- induced by dsRNA, ssRNA, DNA in cytoplasm/endosome by TLRs
- induce positive feedback loop through upregulation of receptors and IFNa/b genes
- can be produced by almost all cell types
Why is interferon release said to be “altruistic”?
-IFN is released by an infected cell, bind to its receptors on neighboring cells, and induce an anti-viral state in them as a form of protection
List 3 examples of proteins induced by IFN to produce an anti-viral state and these proteins effects
- Protein kinase R (PKR): phosphorylates EF2a and inhibits translation
- Rnase L: degrades all mRNA in cell
- Mx protein: binds to some viral proteins and inhibits virus assempby: transcriptional inhibition and inhibition of virus assembly
Viruses that cause acute infections usually inhibit ___________ or ____________ or _________via many mechanisms. The balance between host defense and viral offence determines virulence.
- IFN production or the response to IFN
- apoptosis
Characteristics of chronic viral infections
- virus particles or products are made for prolonged periods of time, continuously or intermittently
- often but not always caused by DNA virus
- may be ultimately cleared, but some remain for lifetime
For a virus to persist and be a chronic infection, it must shutdown what activities that it may encode?
- lethal/cytolytic; become noncytopathic
- **Virus lifestyle: live and let live, stay under the radar
Viruses that cause chronic infections in vivo are usually non-cytopathic in vitro. Explain.
-actively produce new virions without killing the cell
Disease symptoms of chronic viral infections are often the result of what?
-the immune response that kills infected cells
Viruses that cause chronic infections have to exist in the face of an evolving _________. They do so via what 3 mechanisms?
- adaptive immune response
1. viruses can mutate and evolve, staying ahead of the immune response
2. produce proteins that modify the immune response
3. establish a latent infection and wait for immune response to subside
Give an example of how a virus can modify the host immune response as a way of establishing a chronic infection.
- encode proteins that down-regulate MHC class I proteins
- can block this along any step of MHC class I formation and surface production
Latent infections are largely a property of _______ viruses.
-herpes
Describe the protein production of a latently infected cell. What can reactivate these cells?
- cell either makes no virus proteins, or only a few that keep it in latent state
- no protein production= cell is not seen as being infected by immune system
- cells can be reactivated by stress, decrease in immune surveillance
Give 2 examples of latent infections
- HSV and cold sores
- varicella zoster causing chicken pox in child and shingles in later life
What are common sources of virus?
- most human infections are caused by viruses that only infect humans, and so infected humans are often the course of the virus
- viruses can infect animals which can spread it
- viruses can be spread by insects that spread it from animals to humans as well
List 4 different routes of transmission. Which is the most common?
- skin/mucous membrane
- urogenital tract
- Alimentary tract
- respirtatory tract** most common route of viral entry
2 ways viruses are spread via respiratory tract as a route of transmission
- aerosolized droplets frequently contain viruses: rhinoviruses, influenza, coronaviruses, adenoviruses
- infection can also spread via infected saliva