HEPATITIS VIRUSES

Main site of infection is the liver. These five are hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV, delta virus), and hepatitis E virus (HEV)

2018-05-28 22 44 07

Hepatitis A Virus

Summary of Replicative CycleHAV has a replicative cycle similar to that of poliovirus

PathogenesisThe virus replicates in the GI tract and then spreads to the liver during a brief viremic period. The virus is not cytopathic (does not harm) for the hepatocyte. Hepatocellular injury is caused by immune attack by cytotoxic T cells. Virus excreted in the stools for 2 weeks preceding onset of symptoms

 

Hepatitis B Virus

CharacteristicsIncomplete circular double-stranded DNA (i.e., one strand has about one-third missing and the other strand is “nicked” [not covalently bonded]). DNA polymerase in virion. HBV-encoded polymerase acts as a reverse transcriptase by using viral mRNA as the template for the synthesis of progeny genome DNA.

There are three important antigens: the surface antigen(HBsAg), the core antigen (HBcAg) – The core antigen forms the nucleocapsid core of the virion, and the e antigen (HBeAg)- is secreted from infected cells into the blood. The e antigen is an important indicator of transmissibility. In the patient’s serum, long rods and spherical forms composed solely of HBsAg predominate. HBV has one serotype based on the surface antigen.

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Summary of Replicative Cycle

  • After entry of the virion into the cell and its uncoating
  • Carries Reverse Transcriptase enzyme that completes the single stranded DNA portion to form double strand
  • The virion DNA polymerase synthesizes the missing portion of DNA, and a double-stranded closed-circular DNA is formed in the nucleus.
  • This DNA serves as a template for mRNA synthesis by cellular RNA polymerase.
  • After the individual mRNAs are made, a full-length positive-strand transcript is made, which is the template for the minus strand of the progeny DNA.
  • The minus strand then serves as the template for the plus strand of the genome DNA.
  • This RNA-dependent DNA synthesis catalyzed by reverse transcriptase encoded by HBV takes place within the newly assembled virion core in the cytoplasm.
  • The RNAdependent DNA synthesis that produces the genome and the DNA-dependent DNA synthesis that fills in the missing portion of DNA soon after infection of the next cell are carried out by the same enzyme (i.e., the HBV genome encodes only one polymerase).
  • Hepadnaviruses are the only viruses that produce genome DNA by reverse transcription with mRNA as the template. (Note that this type of RNA-dependent DNA synthesis is similar to but different from the process in retroviruses, in which the genome RNA is transcribed into a DNA intermediate.)
  • Some of the progeny DNA integrates into the host cell genome, and this seems likely to be the DNA that maintains the carrier state.
  • Progeny HBV with its HBsAg-containing envelope is released from the cell by budding through the cell membrane.

NB: There is a high incidence of hepatocellular carcinoma (hepatoma) in many Asian countries—a finding that indicates that HBV may be a human tumor virus. It appears that the HBV vaccine is the first vaccine to prevent a human cancer.

PathogenesisHepatocellular injury due to immune attack by cytotoxic (CD8) T cells. Antigen–antibody complexes cause arthritis, rash, and glomerulonephritis. About 5% of HBV infections result in a chronic carrier state. Chronic hepatitis, cirrhosis, and hepatocellular carcinoma can occur. Hepatocellular carcinoma may be related to the integration of part of the viral DNA into hepatocyte DNA.

Virus enters blood circulation – infects epatocytes – viral antigens displayed on hepatocytes – cytotoxic T cells mediate an immune attack against the viral antigens – inflammation and necrosis occurs

Clinical Findings

  • Many HBV infections are asymptomatic and are detected only by the presence of antibody to HBsAg.
  • The incubation period for hepatitis B is 10 to 12 weeks, which is much longer than that of hepatitis A (3–4 weeks).
  • Compared to HAV, hepatitis B, symptoms tend to be more severe, and life-threatening hepatitis can occur.
  • Patients coinfected with both HBV and human immunodeficiency virus (HIV) may have increased hepatic damage if HIV is treated prior to treating HBV. This occurs because the immune reconstitution that results when HIV is treated successfully leads to increased damage to the hepatocytes by the restored, competent cytotoxic T cells. For this reason, it is suggested that HBV be treated prior to treating HIV.

 

Hepatitis C Virus

Summary of Replicative Cycle – The replication of HCV is like other flaviviruses

PathogenesisHepatocellular injury caused by cytotoxic T cells. HCV replication itself does not kill cells (i.e., does not cause a cytopathic effect). More than 50% of infections result in the chronic carrier state. The chronic carrier state predisposes to chronic hepatitis and to hepatocellular carcinoma.

 

Hepatitis D Virus

CharacteristicsDefective virus that uses hepatitis B surface antigen as its protein coat. HDV can replicate only in cells already infected with HBV (i.e., HBV is a helper virus for HDV). HDV has one serotype (because HBV has only one serotype).

Pathogenesis—Hepatocellular injury probably caused by cytotoxic T cells. Chronic hepatitis and chronic carrier state occur.

 

Hepatitis E Virus

Causes outbreaks of hepatitis, primarily in developing countries. Similar to hepatitis A virus in the following ways: transmitted by fecal–oral route, no chronic carrier state, no cirrhosis, and no hepatocellular carcinoma. No antiviral therapy and no vaccine. HEV is a nonenveloped, single-stranded RNA virus

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