Molecular Epidemiology Research Of Human Pegiviruses(HPgVs) Among HIV-1 Infected Individuals In Yunnan Province

Human pegivirus-1(HPgV-1),also known as GB virus C(GBV-C)/hepatitis G virus(HGV),is a positive-sense single-stranded RNA(ssRNA)virus that has recently been classified under the Pegivirus(pe,persistent;g,GB or G)genus of the Flaviviridae family.HPgV-1 is a nonpathogenic human virus.However,co-infection with HIV-1 may result in favorable outcomes such as lower mortality rate,slower disease progression,and longer survival.The genotypic diversity of HPgV-1 may play a role in modulating disease progression in HIV-1-infected individuals.Recently,HPgV-2 was discovered by next-generation sequencing.and it was detected in HIV/HCV co-infected individuals.The Yunnan province is situated in southwest China,borders Southeast Asia countries of Laos,Vietnam and Myanmar to the south.As a hub on the trans-continental drug trafficking road,Yunnan has played a critical role in spreading many blood-borne infections in China.Therefore,it is necessary to study HPgV-1/-2 genotypic diversity and examine its clinical impact in larger cohorts with HIV-1 infection.This present study investigates the prevalence and genotypic diversity of HPgV-1 and its impact on disease progression in 1062 HIV-1-positive patients in Yunnan,China.Firstly,a total of 1062 HIV-1-infected individuals were recruited in all sixteen prefectures of Yunnan province.Nested RT-PCR,phylogenetic analyses,and clinical data analyses were used to detect HPgV-1 infection,determine genotype,and analyze HPgV-1 genotype impact on HIV-1 disease progression.The overall positive rate of HPgV-1 RNA was 23.4%(248/1062),and the frequency of HPgV-1 infection in injecting drug users(IDUs)(28.5%,131/460)was significantly higher than in heterosexuals(19.4%,117/602).Multiple genotypes were identified in 212 subjects with successful sequencing for the E2 gene,including genotype 7(55.7%).genotype 3(34.9%).genotype 4(4.7%).genotype 2(3.3%),and an unclassified group(1.4%).Moreover,genotype 7 predominated in IDUs,whereas genotype 3 was the most common in heterosexuals.Our results revealed that HPgV-1 genotype 7 groups exhibited significantly lower HIV-]viral load and higher CD4-cell counts.Then,for HPgV-1 genotype 4,6 and 7 have the same characteristics of region distribution,and in order to further reveal the evolution and origin relationship within these three genotypes,we successfully obtained 13 full-length genome sequences of HPgV-1 genotype 4 and 7.And results from split network analysis,phylogenetic tree,genetic distence,nucleotide identity and PCOORD proved that genotype 4,6 and 7 share the same evolution and origin and should be classified as one genotype.Thus,we formally provisional designated these three genotypes as genotype 4.What’s more,2 HPgV-1 full-length recombinants were identified and comfirmed by PHI and Bootscanning recombination analysis.Finally,HPgV-2 RNA was detected among 547 HIV-1 infected individuals,including 260 HIV-1 single infection,192 HIV-1/HCV double infection and 95 HIV-1/HCV/HPgV-1 triple infection.And the result found that the infection rate of HPgV-2 was 0.91%(5/547),in which the infection rates for the above three populations were 0.00%(0/260),0.52%(1/192)and 4.21%(4/95),respectively.Besides,4 HPgV-2 full-length genome sequences were successfully amplified and obtained,and phylogenetic analysis based on full-length sequences found that the nucleotide identity of HPgV-2(92.0%,0.058)was higher than HPgV-1(87.5%,0.140)and HCV(66.54%,0.423),respectively.And the clinical data statistical analysis found that there were no difference showed between liver indexes of ALT level and AST level for HPgV-2 infection in HIV-1 infected individuals.In summary,this study revealed the infection rate and genotypic distribution characteristics of HPgV-1 among HIV-1 infected population in Yunnan,and found that HPgV-1 genotype 7 may be associated with a better progression of AIDS disease,and proposed new classification criterion used for HPgV-1.Besides,we also revealed that HPgV-2 was mainly prevalent in HIV-1/HCV coinfected individuals,and described the characteristics of HPgV-2 full-length genome sequences.These work providing important scientific basis for further research the influence mechanism of HPgVs diversity on the progression of HIV-1 disease.