Exploring the biological basis of hepatitis B e antigen in hepatitis B virus infection

Abstract

The function of the hepatitis B e antigen (HBeAg) is largely unknown because it is not required for viral assembly, replication, or infection. In this report we chronicle clinical and experimental studies in an attempt to understand the role of HBeAg in natural infection. H epatitis B virus (HBV) infects more than 300 million people and is a major cause of acute and chronic liver disease in the world. HBV infection has been linked unequivocally to the development of hepatocellular carcinoma. Since the discovery of HBV nearly 3 decades ago, great strides have been made not only in characterizing the molecular biology and immunology of HBV infection, but also in defining the mechanisms of pathogenesis in hepatitis B. However, a few areas of HBV remain highly controversial and/or largely undefined. The biologic function of hepatitis B e antigen (HBeAg) has been such an area of intense research. HBeAg is an accessory protein of HBV, not required for viral replication but important for natural infection in vivo. In this report, we discuss the current state of knowledge and highlight the recent advances in understanding this intriguing gene product, mostly in the context of natural HBV infection and its associated disease.

The phenotype of hepatitis B virus-specific T cells differ in the liver and blood in chronic hepatitis B virus infection

“…The increased frequency of IL-10 -producing T cells within the liver may be a mechanism to protect against hepatic cell destruction and limit liver damage. 22,23 One potential weakness of our methodology was that the effects of culturing T cells from blood and liver may not be identical. It is possible that "exhausted" HBV-specific T cells may have been primed for apoptosis after stimulation, and the extent of exhaustion may differ between intrahepatic and circulating T cells.…”

“…The HBeAg protein has previously been shown to be a tolerogen possibly leading to an anti-inflammatory state as the body attempts to minimize liver damage. 22 Fig . 5.…”

Hepatitis B-specific T helper cell responses in uninfected infants born to HBsAg+/HBeAg− mothers

“…[5][6][7] Identified risk factors for the development of infection include high maternal perinatal viremia and the transplacental passage of HBeAg. 8,9 Both infected and uninfected infants have been shown to encounter HBeAg in utero, but exposure to hepatitis B core antigen (HBcAg), which would indicate possible exposure to virions, has not been documented in babies of either HBeAg 1 or HBeAg 2 mothers. 8,10 Prevention of mother-to-infant transmission has been largely achieved by the administration of passive hepatitis B immunoglobulin and active immunoprophylaxis to all neonates born to carrier mothers.…”

“…8,9 Both infected and uninfected infants have been shown to encounter HBeAg in utero, but exposure to hepatitis B core antigen (HBcAg), which would indicate possible exposure to virions, has not been documented in babies of either HBeAg 1 or HBeAg 2 mothers. 8,10 Prevention of mother-to-infant transmission has been largely achieved by the administration of passive hepatitis B immunoglobulin and active immunoprophylaxis to all neonates born to carrier mothers. However, the added benefit of passive immunoprophylaxis in newborns of HBsAg 1 /HBeAg 2 carrier mothers has recently been questioned.…”

Programmed death 1 expression during antiviral treatment of chronic hepatitis B: Impact of hepatitis B e-antigen seroconversion

“…The biological function of HBeAg is not fully understood, as it is not required for virus assembly, infection, or replication. 16 HBeAg and the viral nucleocapsid, hepatitis B core antigen (HBcAg), share Ͼ90% of amino acids and have been found to be cross-reactive at the T-cell level. 17 As HBeAg is secreted from hepatocytes, it is thought that it has a central role as a tolerogen during HBV infection.…”