Fecal-Oral Transmission & NAKED

Virus Family Pathogenesis Sx Dx Tx Notes

HAV Picorna Incub: 2wk-40wk
Enteric mucosa--1' viremia--liver--bile duct--feces
**Liver: lymphoid cell infiltrate, necroses of
parenchymal cells, prolif of Kupffer cells**
Jaundice
Fatigue
Abdominal pain
Loss of appetite
N & D
IgM against HAV Passive immunization w/Ig
Inactivated
Virosomes (VLP)
HAV Vaccine
T mediated: HLA I restricted
Acute
One serotype
Natural host: Human
Severity corr w/lvl of necrosis
HEV Hepe Incub: 2wk-40wk (young-mid aged adult)
Mexico, Central Am, Asia, NE Africa
Recent travel to high HEV areas
Similar to HAV HEV Ab Acute
20% mortality in Pregnant women
One serotype
Blood borne or Sexual contact
Parenteral Transmission & ENVELOPED
Virus Family Pathogenesis Sx Dx Tx Notes
HCV Flavi
(RNA+)
Incub: 6-7wks
HLA-I restricted Tc
responsible for most
liver damage
Acute: mild & vague
NO jaundice
Chronic: Cirrhosis, Liver
failure, Hepatocellular
carcinoma
Used only to
monitor liver dmg
-
Liver enzyme NOT
consistent for Dx
Index of suspicion
HCAb immunoblot, ELISA,
RNA assay
vRNA via RT-PCR
Treat EARLY!!!
PEG-IFN + ribavirin
Most common chronic blood borne infection
aka. Post transfusion hepatitis
At least 9 genotypes; 1 being most common
21% of all acute hep; 70% chronic
Leading cause of liver transplant
Infection comes from: tattoos, piercing,
shared razor blades, shared toothbrush,
manicures, snuffed cocaine
HGV Flavi
(RNA+)
Blood borne
Transplant recipients
Vertical, Sexual, shared
contam items
**No obvious imm resp
to HGV**
Almost none RT-PCR None Infections are PERSISTENT
Using HBsAg/cAg/eAg & Abs to determine
stage of HBV infection
HBV Hepadna
(partial
dsDNA)
N, F, Joint Pn, Jaundice,
Hx with IV drugs Recombinvax HB
Engerix-B
HBV vaccines:
Tx:
PEG-IFN + Lamivudine
Acute: mile or severe
5% chronic
HDV Delta
(ssRNA-) Simultaneous
Coinfect w/HBV
HBV 1st
HDV later
Superinfect w/HBV
Exacerbates HBV inf HBV vaccine will also
protect against HDV
Virus-like
Interact with JAK-STAT & cellular translation pathways
Blocks IFN signaling (can't tell rest of body that it's infected)
Loss of tumor suppressor kinase PKR-->carcinogenesis
NS5A protein 1.
Blocks innate imm pathway that recognizes viral infection
CD80/86 to activate T-cells
IL-6 & IL-12 are proinflammatory
RANTES: induce migration T/B cells
IFN & ISG normal fxn:
NO IFN or IFN stimulated genes (ISG) activated
NO activation of NFkB or IRF3
NS3/4a protease 2.
HCV remain chronic mainly with two proteins:
Increase errors made by polymerase to generate mutations in vital
genes of virus

Ribavirin
TT to TC change in gene that encodes IFN-3 protein
SNP (single nucleotide polymorphism) has been ID for HCV
Biomarkers for HCV infection
HCV
Evade immune sys
Persistence of virus
Clades=Nucleotide sequences of same genotype in diff countries had
substantial sequence diversity
Env prot has hypervariable regions--multiple HCV variants (Quasi-species)
Latency up to 20yrs
20% coinfect w/HGV
Virion=Dane particle
With same surf mlc as Dane
Bind to Ab so Dane can escape
Decoy=subviral particle
Partial duplex genome (complete DNA- & incomplete DNA+)
HBsAg=envelop
HBcAg=core/capsid
HBeAg=secreted; indicate actively infectious state
HBV
HBcAg & HBeAg
Two AUGs (stop codon) in core ORF
Sent to ER, cleaved to
HBcAg and HBeAg in serum

Capsid
-------------------HBcAg
--------------------------HBeAg
--------------------------------mRNA
-------------pre-C
Superhelical covalenly closed
Virion DNA+ is finished by RT (DNA/RNA-dep DNA
Pol)

DNA- is transcribed into pgRNA (mRNA) by Pol II

pgRNA is transcribed to DNA- by RT
DNA+ is translated by Pol II
Assembly occurs before DNA+ finishes
Replication of HBV
HBsAg has 3 forms:
PreS2 has sequence for receptor binding
Dane have L forms
Thus, can't bind & not infectious
Subvirals do not have L forms
Small "a" determinanet
Medium a+PreS1
Large a+PreS1+PreS2
Has HBsAg (pseudotype)
HBV vaccine also protect against HDV
Use HBV env as own
RNA- recogn by Host RNA Pol II
Rolling circle replication
Cleaves individual genome copies from a single long RNA precursor
RNA catalysis (Ribozyme)
Change RNA sequence after it has been made
UGA (stop)-->UGG(Trp)
Only the larger delta Ag can interact with HBV env prot
Change replication to chronic form
Low lvl of delta Ag in cells forever
Inhibits virus replication
Larger HDV Ag
RNA editing
HDV
Hepatitis Virus
Tuesday, September 03, 2013
10:00 AM
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