| Human Pegivirus (HPgV, formerly GBV-C/HGV), a positively single stranded RNA virus (+ssRNA) of the genus Pegivirus within the family Flaviviridae, which is the most prevalent non-pathogenic RNA virus worldwide, has been reported to be associated with reduced morbidity and mortality in HIV-infected individuals. The mechanisms by which HPgV modulated HIV infection include direct interference with HIV entry and replication and indirect regulation of host factors that ameliorate disease progression. Phylogenetic analysis suggested the existence of five HPgV genotypes with an extent of geographic specificity and variable beneficial effects on HIV disease progression. Due to the shared transmission routes, namely through patenteral transmission, sexual contact and vertical transmisiion, the presence of HPgV in HIV-1 infected population was reported to be 17-41%. The HIV/HPgV coinfected individuals may represent an interesting model for the investigation of the role by HIV infection and/or the immune system in driving the evolution of the HPgV viral populations.The present study investigated the prevalence and population dynamics of HPgV in HIV infected individuals representing 13 geographic regions of Hubei province of China. Approximately 36.5% of 156 HIV-infected individuals were infected with HPgV. Phylogenetic tree was reconstructed by E2 sequence from 33 patients and it revealed that genotype 3 was appeared to be predominant in Hubei proviece and just four patients were infected with genotype 2. Utilizing the E2 sequence from 10 HIV/HPgV infected individuals and employing coalescence based phylogenetic approaches, the present study revealed patient-specific unique HPgV viral lineages and most viral lineages showed the evidence of rapid population expansion in respective HIV-infected patients, thus suggesting HIV was unlikely to have been inhibiting effect on the HPgV viral replication. HPgV in all patients had experienced intense purifying selection, suggesting the HPgV viral invasion and subsequent expansion within the HIV-infected host without any modification of the functional epitopes at their membrane protein, which might be influenced by the destroyed immune system in HIV-1 infected individuals or the weakly immune response against the non-pathogenic HPgV. The finding of within-host HPgV recombinant sequences indicated recombination was one of the significant forces in the evolution and divergent of HPgV. Interestingly, the male-biased genetic recombination in HPgV (7 males vs 1 female) is correlated with the previously available statistical data of higher incidence of male promiscuity than the female promiscuity. Concordantly, our results also revealed that while male patients shared the viral strains with several other patients, viral strains from the femal patients had restricted dispersal. The present study revealed that multiple infections with divergent of HPgV viral strains likely led to within-host genetic recombination, predominantly in male patients, and therefore is the major driver in shaping genetic diversity of HPgV.Despite of the fact that HPgV genotypes might confer different degree of protection against HIV, the lack of clustering as a unique group based on the sequence difference in the antigenic site (267-298aa) among the genotypes suggested some other genomic regions or secondary structure of E2 protein might have played a crucial role in determining the variable protecting effects of HPgV against HIV infection. Furthermore, we evaluated the inhibitory potency of peptides of different genotypes and regions.In conclusion, it is essential to investigate the the evoluntionary pattern in the context of the HPgV and HIV-1 that simultaneously circulate within human population, and the genetic diversity of immunogenic domains and inhibitory potency of peptiede from different genotypes and regions, which may facilitate our understanding about the mechanism responsible for inhibiting HIV replictation by HPgV and provide new therapeutic strategies for HIV infection. |
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