I&I viral replication, pathogenesis
Terms
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- Steps in Viral replication
-
attachment
entry & uncoating
replication
assembly
release - attachment of HIV
- binds CD4 & co-receptor of T cell
- attachment of EBV
- binds CD3 (complement) receptor on B cell
- attachment of Rabies
- binds ACh R on neuron
- attachment of Influenza A
-
binds sialic acid on epithelial cells
hemagluttination - Attachement of viruses
- random, electrostatic, viral ligand/host R, independent of temp
- Entry & Uncoating of Virus
-
entire virus or nucleocapsid into cytoplasm, then remove capsid
RM endocytosis (both)
Direct penetration (naked)
Fusion (enveloped) - receptor mediated endocytosis
-
for either enveloped or naked
requires low pH to releas from vesicle - direct penetration
- entry for non-enveloped virus (no vesicle)
- fusion
- entry for enveloped virus (no vesicle)
- Methylisoxazole
- interferes with uncoating of Picornavirus
- Amantidine
-
(& Rimantidine)
interfere with uncoating of influenza - Tromantadine
- inhibits penetration of herpes
- Enfuvirtide
- inhibits fusion of HIV w/CD4
- Viral Replication DNA viruses
-
Early- virion DNA
Late- Progeny
Translation depends on capping, splice sites, polyadenylation
End Problem - Early replication
-
part of DNA virus replication
make proteins needed to subvert host machinery
requires DNA dependent RNA polymerase - Late replication
-
part of DNA virus replication
make progeny
requires DNA polymerase
ss virus must synthesize a ds intermediate - End Problem
-
in DNA virus replication
Polyoma & Papilloma are circular- no problem
Adeno- linear, synthesizes primer proteins
HBV uses reverse transcriptase - RNA dependent RNA polymerase
-
carried by all RNA viruses
for replication
(retrovius carries RNA dependent DNA polymerase) - replication of ss +RNA virus
-
ss +RNA reads like mRNA
may make ds intermediate
DNA intermediate can integrate into host - replication of ss -RNA virus
- RNA dependent RNA polymerase to synthesize mRNA from - strand
- replication of segmented ss -RNA virus
-
happens in NUCLEUS
Cap snatching to initiate mRNA synthesis - Cap Snatching
-
segmented ss -RNA virus uses to initiate mRNA synthesis
Capped RNA primers are cleaved from cellular nuclear RNA - replication of ds RNA
- synthesize + strand from - strand of parent
- replication of retrovirus
- use - strand DNA intermediate to make + strand RNA progeny
- Quasi species
-
found in RNA virus
advantage over host b/c always changing
high mutation rate - rare direct viral damage
- fever, HA, rash
- Shutoff
-
Poliovirus
Shuts off host cell machinery
cell dies after virus leaves
virus cleaves complex responsible for cap dependent translation - outcome of non-HIV retro viral infection
- persistant infection
- outcome of HIV, Hep B & C infection
- chronic infection
- latent infection caused by
-
lambda virus in E coli
beta virus in diphtheria
HSV - cellular changes due to viral infection
-
Inclusion bodies- Herpes
Syncytia- Measles
Transformation- leads to tumor
Apoptosis & Cellular Degeneration - Ebola Virus Toxin
- Glycoprotein
- Adenovirus Toxin
- penton
- Rotavirus toxin
- NSP4
- Viral Toxins
-
Ebola- glycoprotein
Adeno- penton
Rota- NSP4 - Viral Escape Mechanisms
-
IFN activates genes in some virus
Escape N ABs & CTLs - ACE-2
- receptor for SARS
- delta ORF
- virulent SARS
- SARS
-
coronaviridae
ACE-2 is R
delta ORF was mutation
never efficient enough to switch to human host
reservoir is bat - Influenza
-
8 segments in genome
surface GPs (HA & NA)
HA is fusion prot
NA cleaves sialic acid
protein N1 inhibits IFN activation - Vector Borne Illnesses
-
from Flavivirus
Grippe-like (Dengue) Fever-
fever, bone pain, loss ap
DHF/DSS- shock, cap leak
West Nile, SLE: flu, enceph
Yellow Fever: hem fever, cap
leak, hepatitis