Genetic diversity of hepatitis B virus in Yunnan, China: identification of novel subgenotype C17, an intergenotypic B/I recombinant, and B/C recombinants.

Yunnan is considered to be a geographical hotspot for the introduction, mutation and recombination of several viruses in China. However, there are limited data regarding the genotypic profiles of hepatitis B virus (HBV) in this region. In this study, we characterized 206 HBV strains isolated from chronic hepatitis B patients in Yunnan, China. Initial genotyping based on 1.5 kb sequences revealed that genotype C was the most prevalent at 52.4 % (108/206), followed by genotype B at 30.6 % (63/206) and unclassified genotypes at 17.0 % (35/206). To characterize the 35 unclassified strains, 32 complete HBV genomes were amplified and analysed; 17 isolates were classified within a known subgenotype, 8 were classified as B/C recombinants, 1 was classified as a B/I recombinant and 6 constituted a potentially novel C subgenotype that we designated as C17, based on the characteristics of a monophyletic cluster, >4 % genetic distances, no significant evidence of recombination and no epidemiological link among individuals. Thus, multiple subgenotypes - namely B1, B2, B4, C1, C2, C3, C4, C8 and C17 - and two distinct intergenotypic recombinants exist in Yunnan, China, highlighting the complex and diverse distribution pattern of HBV genotypic profiles.

Characterization of a Novel HIV-1 Circulating Recombinant Form, CRF01_AE/B'/C (CRF96_cpx), in Yunnan, China.

Currently, complex HIV-1 recombinations among the B', C, and CRF01_AE genotypes have frequently arisen in Yunnan, China. A novel HIV-1 complex circulating recombinant form (CRF) consisting of B', C, and CRF01_AE (CRF96_cpx) was recently characterized from three epidemiologically unlinked individuals. Two strains of them were isolated from the injecting drug users in this study, the remaining one strain (JL. RL01) was obtained from a previous report in Jilin province. Phylogenetic analysis based on near full-length genome revealed that CRF96_cpx formed a distinct monophyletic cluster supported by a high bootstrap value of 100%, distantly related to all known HIV-1 subtypes/CRFs. CRF96_cpx had a CRF01_AE backbone with three subtype B' and C segments inserted, respectively, in the gag and pol region. Furthermore, subregion tree analysis showed that CRF01_AE backbone and subtype B segment inserted originated from a Thai-CRF01_AE lineage, whereas subtype C fragment inserted was from an India C lineage. They are different from previously documented CRF01_AE/B/C forms in its distinct backbone, inserted fragment size, and breakpoints. This highlighted the importance of continual monitoring of genetic diversity and complexity of HIV-1 strains in Yunnan, China.

Regulated Entry of Hepatitis C Virus into Hepatocytes.

Hepatitis C virus (HCV) is a model for the study of virus-host interaction and host cell responses to infection. Virus entry into hepatocytes is the first step in the HCV life cycle, and this process requires multiple receptors working together. The scavenger receptor class B type I (SR-BI) and claudin-1 (CLDN1), together with human cluster of differentiation (CD) 81 and occludin (OCLN), constitute the minimal set of HCV entry receptors. Nevertheless, HCV entry is a complex process involving multiple host signaling pathways that form a systematic regulatory network; this network is centrally controlled by upstream regulators epidermal growth factor receptor (EGFR) and transforming growth factor ß receptor (TGFß-R). Further feedback regulation and cell-to-cell spread of the virus contribute to the chronic maintenance of HCV infection. A comprehensive and accurate disclosure of this critical process should provide insights into the viral entry mechanism, and offer new strategies for treatment regimens and targets for HCV therapeutics.