4.43 Flashcards by sophie rosen

Hepatitis -

a clinical syndrome characterized by

inflammation of the liver

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hepatocyte cell death releases

—, which causes jaundice

bilirubin

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bilirubin is a biproduct of

heme
metabolism in the liver (where heme
is detoxified)

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Hepatitis viruses have a strong tropism for the liver

and preferentially replicate in the —

hepatocyte

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—% of liver cells are hepatocytes

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Therefore these viruses primarily cause

liver

disease

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Infectious hepatitis (A and E) (2)

Hit and run

Fecal-oral

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Serum hepatitis (B, C, and D) (2)

Hide and infiltrate

Blood & sexual fluids

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virus: hep A
nucleic acid composition:
virus family:

linear + ssRNA

picornaviridae

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Hepatitis A

characteristics (4)

• infectious hepatitis
• HAV
– icosahedral, naked capsid virus
– positive strand linear RNA

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Hepatitis A

• spread by

fecal-oral contamination of food, drink, or

shellfish

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HAV shed into bile ducts and into intestine and

passes out of the body in the feces

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HAV directly kills —

hepatocytes

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HAV

•clinical manifestations (2)

–usually mild intestinal infection

–occasionally viremia occurs, leading to liver infection (jaundice)

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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

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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

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virus: hep B
nucleic acid composition:
virus famiy:

nicked circular, mostly dsDNA

hepadnaviridae

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Hepatitis B

characteristics (2)

Enveloped

Smallest viral genome: 3200 nucleotides

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Hepatitis B

3 distinct viral particles

–22 nm particle
–Variable tubular/filamentous particle (22 nm diameter)
–42 nm Dane particle (infective form of virus)

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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