Hepatitis B virus

Hepatitis B Virus (Draft)

Higher order taxa Virus; Retro-transcribing viruses; Hepadnaviridae; Orthohepadnavirus

Species Hepatitis B virus

Description and significance

Hepatitis B virus (HBV) causes hepatitis B infection, also known as serum hepatitis. Hepatitis B is one of the most common infectious diseases in the world. Each year an estimated 300,000 people in the United States are infected with HBV. About 5,000 people die yearly from hepatitis-related cirrhosis and about 1,000 die from HBV-related liver cancer. Worldwide, HBV infects over 200 million people.

This virus is normally transmitted through blood transfusions, contaminated equipment, drug users' unsterile needles, or any body secretion (saliva, sweat, semen, breast milk, urine, feces). The virus also can pass from the blood of an infected mother through the placenta to infect the fetus.

Hepatitis B occurs in both acute and chronic forms and may range from mild to severe. Many people infected with HBV never develop any symptoms and may not even know they carry the virus in their bodies; nevertheless, they are still able to pass the virus on to other people. Such people are said to be carriers of the disease. About 1.5 million Americans are thought to be carriers of HBV.

Genome structure

HBV is a mostly double-stranded DNA virus classified as Orthohepadnavirus within the Hepadnaviridae family. HBV causes hepatitis in human and related viruses in this family cause hepatitis in ducks, ground squirrels and woodchucks. The HBV genome has four genes: pol, env, pre-core and X that respectively encode the viral DNA-polymerase, envelope protein, pre-core protein (which is processed to viral capsid) and protein X. The function of protein X is not clear but it may be involved in the activation of host cell genes and the development of cancer.

Cell structure and metabolism

The hepatitis B virus is a complex virus with a central core and a protein coat. The virions of Hepatitis B virus are 42 nm in diameter and possess an isometric nucleocapsid, the core, of 27nm in diameter, surrounded by an outer coat approximately 4 nm thick. The protein of the virion coat is known as "surface antigen" or HBsAg. The surface antigen is sometimes extended as a tubular tail on one side of the virus particle. Produced generally in vast excesses, it is found in the blood of infected individuals in the form of filamentous and spherical particles. Filamentous particles are identical to the virion tails in that they vary in length and have a mean diameter of about 22nm. They sometimes display regular, non-helical transverse striations.

Ecology

Pathology

HBV may cause acute and chronic hepatitis, cirrhosis, hepatocellular carcinoma, immune complex disease, polyarteritis, glomerulonephritis, infantile papular acrodermatitis and aplastic anemia. An asymptomatic carrier state with high viremia may develop particularly after perinatal infection or under immune suppression.

HBV causes acute and chronic hepatitis. The chances of becoming chronically infected depends upon age. About 90% of infected neonates and 50% of infected young children will become chronically infected. In contrast, only about 5% to 10% of immunocompetent adults infected with HBV develop chronic hepatitis B. In some individuals who become chronically infected, especially neonates and children, the acute infection will not be clinically apparent.

Acute hepatitis B can range from subclinical disease to fulminant hepatic failure in about 2% of cases. Many acutely infected individuals develop clinically apparent acute hepatitis with loss of appetite, nausea, vomiting, fever, abdominal pain and jaundice. In cases of fulminant hepatic failure from acute HBV infection, orthotopic liver transplantation can be life-saving. About 90% to 95% of acutely infected adults recover without sequelae. About 5% to 10% of acutely infected adults become chronically infected. The natural history of chronic HBV infection can vary dramatically between individuals. Some will develop a condition commonly referred to as a chronic carrier state. These patients, who are still potentially infectious, have no symptoms and no abnormalities on laboratory testing. Nonetheless, some of these patients will have evidence of hepatitis on liver biopsy.

Some individuals with chronic hepatitis B will have clinically insignificant or minimal liver disease and never develop complications. Others will have clinically apparent chronic hepatitis. Some will go on to develop cirrhosis. Individuals with chronic hepatitis B, especially those with cirrhosis but even so-called chronic carriers, are at an increased risk of developing hepatocellular carcinoma (primary liver cancer). Although this type of cancer is relatively rare in the United States, it is the leading cause of cancer death in the world, primarily because HBV infection is endemic in the East. Chronic infection with HBV can be either "replicative" or "non-replicative." In non-replicative infection, the rate of viral replication in the liver is low and serum HBV DNA concentration is generally low and hepatitis Be antigen (HBeAg) is not detected. HBeAg is an alternatively processed protein of the pre-core gene that is only synthesized under conditions of high viral replication. In "replicative" infection, the patient usually has a relatively high serum concentration of viral DNA and detectable HBeAg. Patients with chronic hepatitis B and "replicative" infection defined by the presence of detectable HBeAg have a generally worse prognosis and a greater chance of developing cirrhosis and/or hepatocellular carcinoma than those without HBeAg. In rare strains of HBV with mutations in the pre-core gene, "replicative" infection can occur in the absence of detectable serum HBeAg.

In its most serious forms, hepatitis B can be a life-threatening disease. The virus causes severe scarring of the liver. The scarring process is called cirrhosis (pronounced suh-RO-suss) of the liver. Cirrhosis damages the liver so badly that it may no longer be able to function normally. It can cause the death of the patient. Cirrhosis can also lead to liver cancer (see cancer entry).

Application to Biotechnology

Current Research

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