Lecture 22: Virus offence meets host defense. Flint et al. Chapter 15, pp. 531 – 584. Note: immunopathology not covered General points We literally swim in viruses and other microbes We’ve evolved numerous, ovelapping active and passive defenses to enable us to ward off infection
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For every host defense, there is a viral offense.
Keeps “wrong” cells from proliferating
“Sacrifice the one for the good of the many”
Promoted by Capsases: Cysteine proteases that cleave after ASPartate residues
Extrinsic pathway: triggered from outside
Intrinsic pathway: triggered from inside
Viruses can alter gene expression inside and outside of cell
Viruses can activate either pathwayApoptosis
Many viral proteins have evolved to inhibit apoptosis by intervening at any one of multiple steps in the pathway.
Pkr (dsRNA activated protein kinase)
Activated by dsRNA.
Phosphorylates eIF2-a, shutting down translation.
Many viral proteins evolved to inactivate or misdirect Pkr.
RNase L + 2’-5’ Oligo(A) synthetase
Work together to degrade RNAs.
Both antiviral and apoptotic
In mice, specifically prevents “cap-snatching” by influenza
In humans ,can also prevent replications of VSV, Measles, parainfluenza and others.
Block cell proliferation
Inhibit rRNA transcription and ribosome biosynthesis
Nitric oxide synthase
Directs synthesis of NO in NK cells
Inhibits poxvirus and herpesvirus replication
Part of the ND10 bodies, prevents transcription of foreign DNA
Ubiquitin-proteosome pathway components
Proteins tagged with ubiquitin are targeted to the proteosome for degradation