Hepatitis B

Question 1

Hepatitis

Answer 1

Disease of the liver. Symptomology varies from malaise, anorexia, and nausea to acute life threatening liver failure. Infects hepatocytes. Regeneration of liver cells can occur, but rapid regeneration leads to fibrosis/cirrohsis. Five known viruses cause hepatitis.; 10 X more infectious than HIV

Question 2

Hepatitis A

Answer 2

ssRNA (+), enterovirus (picornavirus)

Question 3

Hep B

Answer 3

dsDNA, hepadnavirus

Question 4

Hep C

Answer 4

ssRNA (+)

Question 5

Hep D

Answer 5

small circular ssRNA virus; defective virus which required hep B for replication

Question 6

Hep E

Answer 6

ssRNA (+)

Question 7

Hep B

Answer 7

Partially double stranded DNA molecule; full length negative strand and a partial length positive strand; full length negative strand is complementary to viral mRNA; DNA is linear, but arranged in a circle with a specific gap in the + strand; Gap region in - strand has 2 repeated sequences that encodes for pAn site and a potential promoter sequence that reads in a clockwise manner core, S polymerase (envelope proteins), and X protein; genome N/3’/polyA tail terminal ends are the same, but C/5’ terminal ends are different

Question 8

RDDP

Answer 8

Reverse Transcriptase

Question 9

Australian Antigen/HBsAG

Answer 9

Overproduced and is sometimes found alone in the blood; used for vaccines

Question 10

Hep B

Answer 10

Very small; produces about 7 proteins; uses some cellular proteins such as Protein Kinase C and Heat Shock Proteins; smallest genome of all known replication competent viruses

Question 11

Virion

Answer 11

Dane particle; enveloped icosahedrons

Question 12

Membrant

Answer 12

Contains 3 membrane associated polypeptides that comprise the HBsAG

Question 13

Capsid

Answer 13

Composed of a single protein (HBcAG)

Question 14

HBeAG

Answer 14

released from core by detergent treatment

Question 15

4 open reading frames that encode 7 proteins

Answer 15

gene C = 2 frames (HBcAG, HBeAG)
gene S = 3 frames (HBsAG, pre S1, pre S2)
gene P = polymerase, DNA polymerase, reverse transcriptase (RDDP), RNase H, and protein primer
gene X = transcriptional activator that is expressed in the liver; important for carcinogenesis because it is responsible for tumor formation

Question 16

Attachment/Penetration/Uncoating

Answer 16

Receptor mediated adsorption, followed by membrane fusion and partial uncoating; viral ligand is HBsAG or the Australian antigen; cell receptor is unknown (Endonexin II? Carboxypeptidase D in ducks/woodchucks)

Question 17

Genome Replication

Answer 17

Following infection the viral genome is converted to closed circular DNA in the nucleus of the infected cell and becomes associated with cellular histones; 3 major unspoiled transcripts with the same polarity, 3’ ends, and polyA tails, but have different 5’ ends; the largest transcript (C-mRNA/3.4 kb) functions as a template for viral DNA synthesis and serves as mRNA for core protein, reverse transcriptase protein, and a polypeptide primer (for the synthesis of the - DNA strand; RNA is packaged in the vision core particle with RDDP and the polypeptide primer for - strand DNA synthesis ( all of these are in the cell cytoplasm); the - strand is the template for + strand synthesis

Question 18

Replication Overview

Answer 18

Virion binds to receptor (HBsAG; unknown cell receptor) and then uncoats (process unknown) and the it goes into the core where is converted into a completed DNA molecule. RDDP is used to make message.

Question 19

HEP B vs Retroviruses

Answer 19

HB packages DNA vs retroviruses RNA
HB uses protein primer for - strand synthesis vs. retroviruses use tRNA
The S gene of HB and envelope gene of retroviruses share no significant homology
Retroviruses integrate into host DNA vs HB is maintained as an episome
**Are not related even though they share some of the same characteristics

Question 20

Prevalence

Answer 20

Liver cancer is the only cancer that hasn’t decreased in prevalence; Acute Hep B is resolved in 90-95% of cases and becomes chronic in 5-10%

Question 21

Acute Infections

Answer 21

Estimated 2 billion people infected with HB and 500 million are chronic carriers
Approximately 300,000 cases in US with 4000 deaths. In developing countries 15% of population infected at birth or during childhood;Incubation period 30-180 days; transmission via blood and sexual contact; 75% are asymptomatic; fulminant he is rare 2-4 mg/uL, elevation in liver function enzymes, antibodies against HB proteins (HBs and HBc), whether IgM(primary) or IgG

Question 22

Chronic

Answer 22

Persistent infection; cirrhosis; HCC

Question 23

HCC

Answer 23

Epi evidence; geographical correspondence ; HCC incidence higher in hep B infected individuals; virus found in 75-85% of all tumors; problem is lack of culture system to grow virus; X gene is often interrupted or missing in HCC with virus replication but required for immortalization transformation; X gene product HBx activates expression of cellular genes by modulating signal transduction pathways and by modulating various cellular transcription factor; Hbx also binds to p53; Hbx may be acting indirectly in cancer development by activating cellular virus replication which activates immune responses and causes chronic liver inflammation; HBx may directly disrupt cellular function by acting as a transcriptional co activator (tumors may develop due to chronic inflammation); p53 stops the cell from replicating stopping it from repairing damage and apoptosis

Question 24

Therapy

Answer 24

Acute infections: None; hep B immune gamma globulin given to newborn of HBsAG positive mothers to prevent/ammeliorate disease
Chronic: Interferon alpha (4 months), Lamivudine(reverse transcriptase inhibitor), adefovir,famciclovir
Vaccine: for high risk groups, infants and children; sub unit vaccine (s gene for HBsAG) in yeast self assembles 3 IM injections with second and third given 1 and 6 months after dose, greater than 95% who receive all 3 doses develop protective immunity