Notes 3.25

I. Interferons (IFN)
>cytokines
>both type 1 and 2 detect virusestranscription and translation of other
cytokines, inflamm. mediators (IL-12 & IL-6)
>IFN recognition triggers Jak-Stat pathway: phosphorylation cascade
a. Type 1 Interferons
i. Interferon-alpha and interferon-beta
*recognize, response to viral parts in cell
-viral motifs in cell cytoplasm (if cells is infected)
-in uninfected dendritic cells, viral motifs in vacuoles
>interact preferentially w/ TLR 3—IFN-beta
>interact preferentially w/ TLR 9,7,8—INF-alpha
b. Type 2 Interferons
i. Interferon-gamma
*similar in action to type 1 IFNs
*also recognizes other intracellular pathogens besides viruses
II. Effects of Interferons
>(1)expression of inflammatory cytokines: IL-1, TNF, IL-6, IL-12
>(2)expression of anti-viral enzymes
a. Halting Protein Production
-transcription: mRNA
*RNase: destroys RNA
-RNase L. degrades mRNA & rRNA
-translation: string of AA
*protein (PKR-initiation factor protein) that disables cell’s own
initiation factor
***RNase L. and PKR need dsRNA to work
b. Halting viral budding from host cell
-Mx proteins expressed: stop blebs of cells membrane from pinching off
c. Viral evasion of interferon effects
*Flu virus makes a protein that covers dsRNAdsRNA then not detected
*Pox viruses stop Jak-Stat phosphorylation cascadeantiviral gene
expression
d. Interferons as disease treatments
-injections of IFN-gamma treat Hepatitis B & C
>viral infection that can cancer
-some virally-caused cancers (Kaposi’s Sarcoma) also treated with IFN-γ
which is caused by HIV
III. Induction of apoptosis
a. p53 pathway
>also signaling pathway (phosphorylation)
>result in mitochondrial release of ions, proteinscells death through
apoptosis
>can be triggered by external stimuli
>can also be triggered by DNA replication out of sync with mitosis
b. Fas ligand and TNF-receptor binding
>binds protein Fas
>Fas binding to FAs ligand alsoapoptosis
>TNF-receptor: TNF binds to TNF receptor on surface of cell, if cell has
stopped protein production, apoptosis results
c. Viral evasion of apoptosis
i. HPV 16 & 18
>HPV types 16 & 18 make E6, a protein that binds to p53
-E6-p53 complex bound by ubiquitin
*ubiquitin binding to any protein marks it for destruction
**Bcl-2: negative feedback for Fas, p53counter apoptosis protein
—HPV16 &18 make transcription factor that increases expression of
Bcl-2
IV. Disabling Viral Nucleic Acids
a. Cytosine deaminases
>Enzymes that remove the NH from cytosine
-CU
*this causes a DNA mutation
*virally-infected cells reduce cytosine deaminases, package into
capsid of retroviruseswhich causes LOTS of mutated CU in
new virions, hopefully destroy ability of virus to replicate
>*HIV makes vif, which ubiquitination and degradation of cytosine
deaminases
b. RNAi
>RNA interferens
>when dsRNA detected (TLR-3), express a gene called “Dicer”, which
cleaves dsRNA into tiny fragments
>another enzyme works with “dicer”, dsRNA fragments recognized by set
of other proteins, which then destroy any ssRNA homologous to dsRNA
fragments

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