Hepatitis B Virus e Antigen Variants - International Journal of Medical Sciences

[Guest guest]

----- Original Message -----

From: " Dr Anita Bay "

> Hepatitis B Virus e Antigen Variants

> Shuping Tong 1, Kyun-Hwan Kim 1, Chante 2, Jack Wands 1, Jisu Li 1

> 1. Liver Research Center, Rhode Island Hospital, Brown Medical School,

> Providence, RI 02903, USA

> 2. Cardinal Santos Medical Center, Metro Manila, 1500, Philippines.

> Int. J. Med. Sci. 2005 2: 2-7 http://medsci.org/v2i1.php#ijmsv02p0002

>

> Abstract: More than 300 million people worldwide are chronically infected

> with

> hepatitis B virus (HBV). Considering the very short generation time for a

> virus, and the high error rate associated with the reverse transcription

> step of HBV replication, decades of HBV infection are probably equivalent

> to

> million years of human evolution. The most important selective force

> during

> the natural course of HBV infection appears to be the immune response. The

> development of anti-HBe antibody in hepatitis B patients usually

> correlates

> with reduction of HBV viremia. As a consequence, escape mutants of

> anti-HBe

> are selected. The core promoter mutants express less HBe antigen (HBeAg)

> through transcriptional down regulation, while precore mutants express

> truncated products. We recently identified additional mutations that

> modulate HBeAg translation initiation, proteolytic cleavage, and secondary

> structure maintenance through a disulfide bond. The core promoter mutants

> have been associated with the development of fulminant hepatitis during

> acute infection and liver cancer during chronic infection. Consistent with

> their enhanced pathogenicity, core promoter mutants were found to

> replicate

> at up to 10-fold higher levels in transfected human hepatoma cells than

> the

> wild-type virus. Moreover, some core promoter mutants are impaired in

> virion

> secretion due to missense mutations in the envelope gene. These

> virological

> properties may help explain enhanced pathogenicity of core promoter

> mutants

> in vivo.

>

> Author biography: Shuping Tong MD, PhD is an Assistant Professor of

> Medicine

> at the Liver Research Center, Rhode Island Hospital, Brown Medical School.

> Dr. Tong was among the first to independently identify the precore mutants

> of HBV, for which he received the " Young Investigator's Award " from the

> French Society for the Study of Liver Diseases in 1989. His major research

> interests are on the molecular properties of naturally occurring HBV

> variants, with regard to gene expression, genome replication, and virion

> secretion.

>

> Jisu Li MD, PhD is an Assistant Professor of Medicine at the Liver

> Research

> Center, Rhode Island Hospital, Brown Medical School. Dr. Li was the first

> to

> demonstrate the biological and clinical significance of HBV genotypes when

> she discovered rare emergence of precore mutants in genotype A strains due

> to a base-pairing requirement of the overlapping pregenome encapsidation

> signal. She is interested in studies on the molecular biology of HCV, the

> duck hepatitis B virus receptor complex, and HBV genotypes.

>

>