4.43 Flashcards
Hepatitis -
a clinical syndrome characterized by
inflammation of the liver
hepatocyte cell death releases
—, which causes jaundice
bilirubin
bilirubin is a biproduct of
heme
metabolism in the liver (where heme
is detoxified)
Hepatitis viruses have a strong tropism for the liver
and preferentially replicate in the —
hepatocyte
—% of liver cells are hepatocytes
85
Therefore these viruses primarily cause
liver
disease
Infectious hepatitis (A and E) (2)
Hit and run
Fecal-oral
Serum hepatitis (B, C, and D) (2)
Hide and infiltrate
Blood & sexual fluids
virus: hep A
nucleic acid composition:
virus family:
linear + ssRNA
picornaviridae
Hepatitis A
characteristics (4)
• infectious hepatitis
• HAV
– icosahedral, naked capsid virus
– positive strand linear RNA
Hepatitis A
• spread by
fecal-oral contamination of food, drink, or
shellfish
HAV shed into bile ducts and into intestine and
passes out of the body in the feces
HAV directly kills —
hepatocytes
HAV
•clinical manifestations (2)
–usually mild intestinal infection
–occasionally viremia occurs, leading to liver infection (jaundice)
HAV
tx (2)
– killed HAV vaccine (now recommended for all in US, esp. for
military, frequent travelers, staff of care facilities)
– Post-exposure immune globulin
In highly endemic regions, almost all children become infected in first few years of life (2)
- most remain asymptomatic
- adults from nonendemic regions who become infected are more likely to display symptoms
virus: hep B
nucleic acid composition:
virus famiy:
nicked circular, mostly dsDNA
hepadnaviridae
Hepatitis B
characteristics (2)
Enveloped
Smallest viral genome: 3200 nucleotides
Hepatitis B
3 distinct viral particles
–22 nm particle
–Variable tubular/filamentous particle (22 nm diameter)
–42 nm Dane particle (infective form of virus)
Embedded in lipid bilayer
(envelope)
— is the main component
HBsAg-S
— is a processed form of the core, HBcAg.
HBeAg
HBeAg is mostly secreted from infected cells and found
in —. Useful marker for —.
bloodstream
HBV infection
–22 nm particle
— is the
main component
HBsAg-S
Variable tubular/filamentous particle (22 nm diameter)
filaments are enriched for —
HBsAg-L
Both types of 22 nm particles are empty
envelopes. Most are —.
Up to — particles per mL!
spherical
10^13
Partially double
stranded DNA
genome; only
— nt in size
3200
RT occurs during
viral
assembly, unlike retroviruses
Reverse transcription is by
viral reverse transcriptase
Priming of reverse transcription by TP (terminal protein domain) of viral
polymerase by
adding first nucleotide to a tyrosine residue of TP
Cell-mediated immune response determines course of
HBV infection
Cytotoxic T
lymphocytes kill
infected —
hepatocytes
HBV does not directly kill hepatocytes
Cytotoxic T lymphocytes directed against MHC
class I proteins bound to viral antigens on
hepatocyte surface
Killing also occurs by
cytokine release that
promotes inflammation and tissue damage
Outcomes of acute HBV infection
–% infants infected with HBV become
chronically infected
90
immature cell-mediated immune response
Hepatocellular carcinoma - why? (2)
increased cell division due to regeneration - increases
chances of mutations
peroxides and free radicals from CTL killing
•treatment, prevention, and control (4)
–vaccination recommended for all infants in USA
–HBsAg particles produced in yeast
–passive immunotherapy within 7 days of exposure
–reverse transcriptase inhibitors (originally anti-HIV drugs)
virus: hep D
nucleic acid composition:
virus family:
Circular - ssRNA
deltaviridae
• hepatitis D virus (HDV)
– Depends on — virus to replicate
HBV
Chronic HBV infection
exacerbated by infection
with
hepatitis delta virus
virus: hep C
nucleic acid composition:
virus family:
linear + ssRNA
flaviviridae
Hepatitis C
characteristics (2)
• enveloped
• In addition to HCV transmission through blood and sexual
fluid, HCV also spreads from mother to fetus, by fecal-oral
route, and through organ transplants
HCV also does not directly kill hepatocytes
Cytotoxic T lymphocytes directed against MHC class I proteins bound to viral antigens on hepatocyte surface
HCV
Killing also occurs by
cytokine release that promotes inflammation and tissue damage
Mixed cryoglobulinemia
immune complex disease of kidney and other sites - disease outside of liver Inflammation and blockage of small and medium blood vessels caused by cryoglobulin deposition
virus: hep E
nucleic acid composition:
virus family:
linear + ssRNA
caliciviridae
hep E
Not budding; released
as a
naked capsid
virus
Hepatitis E
• spread in
contaminated food and drink (like HAV)
Hepatitis E
transmission
• human-to human transmission and animal-to-human
transmission (common source = pigs) (zoonosis).
HEV shed into
HEV directly kills —
bile ducts and into intestine and passes out of the body in the feces
hepatocytes
