Molecular, immunological and clinical properties of mutated hepatitis B viruses

Abstract

Hepatitis B virus (HBV) is at the origin of severe liver diseases like chronic active hepatitis, liver cirrhosis and hepatocellular carcinoma. There are some groups of patients with high risk of generation of HBV mutants: infected infants, immunosupressed individuals (including hemodialysis patients), patients treated with interferon and lamivudine for chronic HBV infection. These groups are the target for molecular investigations reviewed in this paper. The emergence of lamivudine‐ or other antiviral‐resistant variants, rises concern regarding long term use of these drugs. Infection or immunization with one HBV subtype confers immunity to all subtypes. However, reinfection or reactivation of latent HBV infection with HBV mutants have been reported in patients undergoing transplant and those infected with HIV. Mutations of the viral genome which are not replicative incompetent can be selected in further course of infection or under prolonged antiviral treatment and might maintain the liver disease. Four open reading frames (ORF) which are called S‐gene, C‐gene, X‐gene and P‐gene were identified within the HBV genome. Mutations may affect each of the ORFs. Mutated S‐genes were described to be responsible for HBV‐infections in successfully vaccinated persons, mutated C‐genes were found to provoke severe chronic liver diseases, mutated X‐genes could cause serious medical problemes in blood donors by escaping the conventional test systems and mutated P‐genes were considered to be the reason for chemotherapeutic drug resistance. This paper reviews molecular, immunological and clinical aspects of the HBV mutants.

Molecular Characteristics of Occult Hepatitis B Virus from Blood Donors in Southeast China

“…Individuals with OBIs are defined as those in whom viral DNA is detected in liver or blood by nested PCR or real-time PCR but in whom HBsAg is undetectable in serum by current commercial HBsAg assays. Occult HBV infection status can be associated with mutant viruses undetectable by current HBsAg assays (10,11,15,17,28), but it may also be due to the suppression of viral replication and gene expression and virus secretion (2,7,13,23). The presence of an OBI can occur after recovery from an infection but anti-HBs remains present (21,25,29) or anti-HBc is the only marker (12), or an OBI may even be the state in which no antibody makers may be present.…”

Identification of Novel D11 Hepatitis B Surface Antigen Subgenotype in Jeddah, Kingdom of Saudi Arabia

“…Existence of HBV quasi-species (Schatzl et al, 1997) has facilitated the development of mutants with specific ability to escape antibody detection and neutralization. These mutants may lead to reinfection, because it replicates through an RNA intermediate synthesized by reverse transcriptase of viral genomes (Kreutz, 2002;Ohishi et al, 2004) and quasi-species are generated (Torresi, 2002;Liu et al, 2002;Hsu et al, 2004). This resulted in the production of viral mutants during naturally occurring infections (Chong-Jin et al, 1999).…”

Occult hepatitis B virus infection in Egyptian hemodialysis patients with or without hepatitis C virus infection

“…5 Occult HBV is thought to be due to infection with mutant virus that cannot be detected with commercially available molecular methods. 20 Such mutations could result in impaired antigen production by the virus, a diminished rate of replication, or could facilitate viral persistence. 21 Our future studies will examine HBV genotypes to determine whether HBV mutations account for the presence of occult HBV in our hemodialysis population.…”