Hepatitis C and Human Pegivirus Coinfection in Patients with Chronic Hepatitis C from the Brazilian Amazon Region: Prevalence, Genotypes and Clinical Data.

Coinfection of HPgV-1 with hepatitis C virus (HCV) is common due to shared modes of transmission, with a prevalence of HPgV-1 viremia of approximately 20% among individuals with chronic HCV infection. The aim of the present study was to estimate the prevalence of HPgV-1 RNA and circulating genotypes in patients with hepatitis C from a health service located in the city of Belém, in the state of Pará, Northern Brazil. A total of 147 samples were included in the study from February to December 2019. Among the participants, 72.1% (106/147) were monoinfected with HCV, with detectable HCV viral RNA, and 27.9% (41/147) were coinfected with HCV/HPgV-1. The most frequently found genotypes were HPgV-1 genotypes 1 and 2 (36.6% and 63.4%), respectively. While for HCV there was a predominance of genotypes 1 and 3 (58.5% and 41.5%). No significant differences were found when comparing any risk, sociodemographic, or clinical factors between groups. Also, there was no statistically significant difference when relating the viral genotypes of both agents. This study indicated that the prevalence of infection by HPgV-1 is high in HCV carriers in Belém, Pará, and probably does not change the clinical course of HCV infection, however, further studies are still needed.

Human pegivirus (HPgV, GBV-C) RNA in volunteer blood donors from a public hemotherapy service in Northern Brazil.

BACKGROUND: Human pegivirus (HPgV)-formerly known as GBV-C-is a member of the Flaviviridae family and belongs to the species Pegivirus C. It is a non-pathogenic virus and is transmitted among humans mainly through the exposure to contaminated blood and is often associated with human immunodeficiency virus (HIV) infection, among other viruses. This study aimed to determine the prevalence of HPgV viremia, its association with HIV and clinical epidemiological factors, as well as the full-length sequencing and genome characterization of HPgV recovered from blood donors of the HEMOPA Foundation in Belém-PA-Brazil. METHODS: Plasma samples were obtained from 459 donors, tested for the presence of HPgV RNA by the RT-qPCR. From these, a total of 26 RT-qPCR positive samples were submitted to the NGS sequencing approach in order to obtain the full genome. Genome characterization and phylogenetic analysis were conducted. RESULTS: The prevalence of HPgV was 12.42%. We observed the highest prevalences among donors aged between 18 and 30 years old (16.5%), with brown skin color (13.2%) and men (15.8%). The newly diagnosed HIV-1 prevalence was 26.67%. The HPgV genotype 2 (2a and 2b) was identified. No data on viral load value was found to corroborate the protective effect of HPgV on HIV evolution. CONCLUSIONS: This study provided information regarding the HPgV infection among blood donors from HEMOPA Foundation. Furthermore, we genetically characterized the HPgV circulating strains and described by the first time nearly complete genomes of genotype 2 in Brazilian Amazon.

Structural insights into NS5B protein of novel equine hepaciviruses and pegiviruses complexed with polymerase inhibitors.

Infections produced by hepaciviruses have been associated with liver disease in horses. Currently, at least three viruses belonging to the Flaviviridae family are capable of producing a chronic infection in equines: non-primate hepacivirus (NPHV), Theiler's disease-associated virus (TDAV), and equine pegivirus (EPgV). The RNA-dependent RNA polymerases of viruses (RdRp) (NS5 protein), from the flavivirus family, use de novo RNA synthesis to initiate synthesis. The two antiviral drugs currently used to treat hepatitis C (HCV), sofosbuvir and dasabuvir, act on the viral NS5B polymerase as nucleoside and non-nucleoside inhibitors, respectively. Both drugs have shown significant clinical inhibition of viral response. In this work, we aimed to model the NS5B polymerase of the equine hepacivirus (EHCV) subtypes 1 and 2, TDAV and EPgV, to assess whether current direct-acting antiviral drugs against HCV interact with these proteins. Crystal structures of HCV-NS5B were used as templates for modeling target sequences in both conformations (open and closed). Also, molecular docking of sofosbuvir and dasabuvir were performed to predict their possible binding modes at the modeled NS5B polymerase binding sites. We observed that the NS5B models of the EHCV and EPgV shared well-conserved 3D structures to HCV-NS5B and other RdRps, suggesting functional conservation. Interactions of EHCV subtypes 1, 2 and TDAV polymerases with sofosbuvir showed a similar molecular interaction pattern compared to HCV-NS5B, while interactions with dasabuvir were less conserved. In silico studies of molecular interactions between these modeled structures and sofosbuvir suggest that this compound could be efficient in combating equine pathogens, thus contributing to animal welfare.