In presently identified recombinant sequences, we detected the presence of Pc G1896A, and this suggests a possible similar situation and a matter for further investigation. Recent reports suggest the presence of mixed genotypes in Asia. Europe and Africa in CHB patients, including India[9,11,33]. Moreover, higher levels of HBV replication have been shown to be sellectchem associated with mixed genotype infection[33]. It is quite possible that the PreS, core, X and P proteins are continually expressed but the preS2 region/protein of genotype D is lost for a short interval during recombination with genotype A sequences, mimicking a molecular window period. It is not yet known whether recombination is advantageous for the virus or the host, but it is quite possible that this phenomenon increases the chances of virus survival and doping the host defense system.
One of the reasons for enhanced HCC development in young African adults could be high HBsAg expression in genotype-A-harboring patients[34] HBV genotype A directs the high level of synthesis of HBsAg in proportion to viral DNA, core protein and HBeAg[35]. The frequency of detection of spliced viral genomes is higher in CHB cases compared to acute and resolved HBV infections. The generation of recombinant HBV could be intracellular, as the ratio of full-length and spliced genomes isolated from the intracellular compartment was significantly higher than from extracellular space. This indicates that, compared to those containing spliced genomes, nucleocapsids containing full-length genomes are preferentially enveloped and released from the cell, and could be one of the reasons for severe liver disease[36].
It would be worth while to study the co-infection of two genotypes, and to establish whether the changes accumulate in one cell or together in the newly infected cells. Genetic exchanges between different viral strains within the infected hepatocytes could be one of the possible reasons for recombination. HBV infection is the predominant factor for the development of HCC in India[37]. Several reports suggest integration of the preS/S region in cancerous liver tissue[38-40]. Binding of the PreS region with fibronectin and transactivation of TGF �� could lead to development of cirrhosis and HCC[41-43]. It is quite unique that HBV uses its strongest promoter preS2/S for expression of the host cellular genes, which are advantageous for the virus itself.
HBV recombinant sequences were analyzed with the orangutan and gibbon monkey hepatitis virus. However, we could not find Cilengitide any association of recombinant sequences with them, and the reason for such transmission was clarified (data not shown). Secondly, phylogenetic analysis was done using the Italian and Indian recombinant sequences reported previously[27,28].