Virus Host Responses Flashcards
- List effects of viruses on infected cells: CPE, syncytia, growth, apoptosis.
CPE: any detectable morphologic changes in the host cell.
- Direct cell damage / death from: diversion of the cell’s energy, shutoff of cell macromolecular synthesis, competition of viral mRNA for cellular ribosomes, competition of viral promoters and enhancers for cellular factors and inhibition of the interferon defense mechanisms.
- Indirect cell damage can result from integration of the viral genome, induction of mutations in the host genome, inflammation, and host immune response.
Growth can be conferred by an oncogene or by offering some sort of selective advantage
Explain IFN response and “anti-viral state”.
- Characteristic of a cell that has bound and responded to
IFN. The responding cell need not be infected! (optimal state to block viral replication) - Alters transcription of > 100 cellular genes (both ↑ and ↓)
- Facilitated by dsRNA (dsRNA activates a number of IFN responsive genes, and is produced or is an intermediate in the replication cycle of some viruses
- Results in temp blockade of cell proliferation, reduces cellular metabolism, potentiates NK cell activity including γIFN production, increases expression of antigen presentation molecules, may lead to apoptosis, and more
- Most viruses can induce IFN production and therefore cause a common “flu-like” syndrome including fever, chills, nausea and malaise;
- Large amounts of IFN have dramatic physiological consequences (i.e. significant side effects) but have been successful in treatment of some persistent infections (hepatitis C) as well as some tumors
Distinguish between innate and adaptive anti-viral responses.
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Compare antibody characteristics produced in primary and secondary responses
Antibodies produced during primary virus infections are usually of lower affinity than those produced later, and are often of the IgM isotype (unswitched).
List and describe major cell types involved in anti-viral responses.
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Compare the efficacy of antibody versus cell-mediated immunity in the anti-viral response.
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Explain means of virus evasion/manipulation of host defenses by various viruses.
A. Antigenic variation- mechanisms include point mutations in antigenic drift (e.g. HIV, influenza A) and genome shuffling in antigenic shift (e.g. influenza A). These rapid genetic changes allow viruses to become unrecognizable to specific immune receptors.
B. Immune tolerance (molecular mimicry or infection prior to competent immune system). Virus proteins that closely resemble host proteins may escape recognition.
C. Restricted expression of viral genes- going invisible to the host defenses as in latent infections (e.g. HIV).
D. Production of viral molecules that act as inhibitors or decoys of host defense molecules such as cytokines, receptors, and Ab’s (e.g. Pox and Herpesviruses). Viruses produce proteins which can bind and block cellular mediators or can mimic cellular mediators. Those that mimic may have evolved to omit certain functions of their cellular counterparts (such as stimulatory functions) and retain only those functions which benefit them (such as suppressive functions).
E. Down-regulation of host proteins such as MHC class I or adhesion molecules (e.g. Pox and Herpesviruses). Since class I is required for CTL recognition, downregulation protects these virus- infected cells from detection. Class I downregulation however, is a trigger for NK cell detection, so some sophisticated viruses also express a viral homolog of class I molecules to avoid NK recognition.
F. Infection of immunoprivileged sites such as the brain (e.g. HSV).
G. Direct infection of the immune system (e.g. HIV and EBV).
H. Inhibition of apoptosis and cell cycle control (e.g. SV40 large T antigen and Adenovirus E1A). Many viruses affect these two pathways, and these two pathways are also often involved in tumorigenesis.
I. Many more not yet elucidated
