Sequences of 234 complete genomes and 631 hepatitis B surface antigen genes were used to assess the worldwide diversity of hepatitis B virus (HBV). Apart from the described two subgenotypes each for A and F, also B, C, and D divided into four subgenotypes each in the analysis of complete genomes supported by significant bootstrap values. The subgenotypes of B and C differed in their geographical distribution, with B1 dominating in Japan, B2 in China and Vietnam, B3 confined to Indonesia, and B4 confined to Vietnam, all strains specifying subtype ayw1. Subgenotype C1 was common in Japan, Korea, and China; C2 in China, South-East Asia, and Bangladesh, and C3 in the Oceania comprising strains specifying adrq-, and C4 specifying ayw3 is encountered in Aborigines from Australia. This pattern of defined geographical distribution was less evident for D1-D4, where the subgenotypes were widely spread in Europe, Africa, and Asia, possibly due to their divergence having occurred a longer time ago than for genotypes B and C, with D4 being the first split and still the dominating subgenotype of D in the Oceania. The genetic diversity of HBV and the geographical distribution of its subgenotypes provide a tool to reconstruct the evolutionary history of HBV and may help to complement genetic data in the understanding of the evolution and past migrations of man.

Genetic Diversity of Hepatitis B Virus Strains Derived Worldwide: Genotypes, Subgenotypes, and HBsAg Subtypes

Hepatitis B virus (HBV) has evolved a unique life cycle that results in the production of enormous viral loads during active replication without actually killing the infected cell directly. Because HBV uses reverse transcription to copy its DNA genome, mutant viral genomes emerge frequently. Particular selection pressures, both endogenous (host immune clearance) and exogenous (vaccines and antiviral drugs), readily select out these escape mutants. Which particular viral mutations or combination of mutations directly affect the clinical outcome of infection are not known. Further studies are clearly needed to identify the pathogenic basis and clinical sequelae arising from the selection of these mutants.

Molecular virology of hepatitis B virus.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1053/he.2000.6709

Clinical relevance of hepatitis B viral mutations.

Hepatitis B surface antigen (HBsAg) is not only critical to the biology of hepatitis B virus (HBV), it is also the basis of the currently available vaccines, assays to detect it in serum are crucial for diagnosis of infection and antibodies against it are used clinically to suppress infection of transplanted livers. All of these rely on antigenic interactions between HBsAg and HBsAb. Thus, it should not be surprise that changes in epitopes will affect all these situations. It is useful to classify such changes simplistically as variants, found in natural isolates, and mutants, which are observed to emerge, usually under immunological pressure, often medical in origin. The former tend to affect the sensitivity of diagnostic assays and the latter allow escape of viruses in vaccinees and those being treated with HBsAb. The majority of these changes cluster in the hydrophilic central core of HBsAg, from aa99 up to 169. They are gaining importance as causes of mistaken diagnosis and are associated with infection of vaccinees and transplanted livers. There is a danger that they will become the dominant strains as vaccination becomes universal. More data are required on the epidemiology and antigenicity of these changes.

The clinical significance of surface antigen variants of hepatitis B virus

Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite hepatitis B immune globulin prophylaxis.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.510240304

J. Waters

Papers

Hepatitis B virus envelope variation after transplantation with and without hepatitis B immune globulin prophylaxis