Deep sequencing identifies two genotypes and high viral genetic diversity of human pegivirus (GB virus C) in rural Ugandan patients

Abstract

Human pegivirus (HPgV), formerly 'GB virus C' or 'hepatitis G virus', is a member of the genus Flavivirus (Flaviviridae) that has garnered significant attention due to its inhibition of HIV, including slowing disease progression and prolonging survival in HIV-infected patients. Currently, there are six proposed HPgV genotypes that have roughly distinct geographical distributions. Genotypes 2 and 3 are the most comprehensively characterized, whereas those genotypes occurring on the African continent, where HPgV prevalence is highest, are less well studied. Using deep sequencing methods, we identified complete coding HPgV sequences in four of 28 patients (14.3 %) in rural Uganda, east Africa. One of these sequences corresponds to genotype 1 and is the first complete genome of this genotype from east Africa. The remaining three sequences correspond to genotype 5, a genotype that was previously considered exclusively South African. All four positive samples were collected within a geographical area of less than 25 km 2 , showing that multiple HPgV genotypes co-circulate in this area. Analysis of intra-host viral genetic diversity revealed that total single-nucleotide polymorphism frequency was approximately tenfold lower in HPgV than in hepatitis C virus. Finally, one patient was co-infected with HPgV and HIV, which, in combination with the high prevalence of HIV, suggests that this region would be a useful locale to study the interactions and co-evolution of these viruses. The nucleotide sequences reported in this study were deposited in GenBank with accession numbers KC618398-KC618401.

Discovery and Characterization of Distinct Simian Pegiviruses in Three Wild African Old World Monkey Species

“…The Kibale SPgVs are monophyletic and share a most-recent common ancestor with HPgV and SPgV cpz , demonstrating the closely shared evolutionary history of these viruses in a geographic region where HPgV shows significant genetic variability [75]. Analysis of the partial-helicase phylogeny allows for comparison of the genetic diversity of most primate pegiviruses described to date across a well-studies coding sequence: the clades comprising pegiviruses that infect Old versus New World primate species now exhibit similar genetic diversity, while sequences of Kibale SPgV variants from animals of a given species were highly similar (≥94% nt ID).…”

Human pegivirus isolates characterized by deep sequencing from hepatitis C virus‐RNA and human immunodeficiency virus‐RNA–positive blood donations, France

“…Exploration of diversity, distribution, and potential hosts of pegiviruses is in perpetual re‐evaluation . In the case of human infections, at least six genotypes of the virus have been described, typically classified by phylogenetic comparison of 5′‐untranslated region (5′‐UTR), E2, or complete genomic sequences: genotype 1 is retrieved in West Africa, genotypes 1 and 2 in Europe and North America, genotype 3 in parts of Asia, genotype 4 in South East Asia, genotype 5 in South Africa, and genotype 6 in Indonesia; recombination events have also been described …”

“…28,29 In the case of human infections, at least six genotypes of the virus have been described, typically classified by phylogenetic comparison of 5ʹ-untranslated region (5ʹ-UTR), E2, or complete genomic sequences: genotype 1 is retrieved in West Africa, genotypes 1 and 2 in Europe and North America, genotype 3 in parts of Asia, genotype 4 in South East Asia, genotype 5 in South Africa, and genotype 6 in Indonesia; recombination events have also been described. [30][31][32][33][34][35] Despite those advances, precise analysis of the literature reveals very poor information regarding HPgV nucleotide (nt) sequences characterized in France up to now. Thus, genomic information relative to previous epidemiological studies is mostly reduced to a set of short-viral sequences 7 ; this lack of genetic data is also exemplified by the availability in the GenBank database of a unique full-length coding sequence of a French genotype 2 isolate of HPgV characterized in 1998 (GenBank accession no.…”

Use of Flaviviral genetic fragments as a potential prevention strategy for HIV-1 Silencing

“…On the other hand, if HIV-1 entry is blocked by the extracellular event, as has been proposed by various groups [12,37], whereby the Flaviviridae NS5-protein or E2 Abs may be interfering with HIV-1 entry, then it is likely interfering with step 1; either by blocking the HIV-1 binding sites (i.e., CD4, CCR5, or CXCR4 molecules) by structural mimicry, or through indirect interference at the entry sites [14]. Obviously, this would not be a logical explanation since only pegiviruses infect T-and B-lymphocytes and other members of the Flaviviridae do not infect CD4+ T lymphocytes [3].…”

“…GBV-C is a close relative of GB virus A, GB virus B, and HCV. Pegiviruses are known to be non-pathogenic [13,14]. We propose the development of a recombinant GBV-C-based viral vaccine that can incorporate the major "beneficial anti-HIV-1 genetic fragments" that can serve as a preventive vaccine against HIV-1.…”