PMID- 32750098 OWN - NLM STAT- MEDLINE DCOM- 20201014 LR - 20220110 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 15 IP - 8 DP - 2020 TI - Diversity of the hepatitis C virus NS5B gene during HIV co-infection. PG - e0237162 LID - 10.1371/journal.pone.0237162 [doi] LID - e0237162 AB - Viral diversity is an important feature of hepatitis C virus (HCV) infection and an important predictor of disease progression and treatment response. HIV/HCV co-infection is associated with enhanced HCV replication, increased fibrosis, and the development of liver disease. HIV also increases quasispecies diversity of HCV structural genes, although limited data are available regarding the impact of HIV on non-structural genes of HCV, particularly in the absence of direct-acting therapies. The genetic diversity and presence of drug resistance mutations within the RNA-dependent RNA polymerase (NS5B) gene were examined in 3 groups of women with HCV genotype 1a infection, including those with HCV mono-infection, antiretroviral (ART)-naive women with HIV/HCV co-infection and CD4 cell count <350 cells/mm3, and ART-naive women with HIV/HCV co-infection and CD4 cell count >/=350 cells/mm3. None had ever been treated for HCV infection. There was evidence of significant diversity across the entire NS5B gene in all women. There were several nucleotides and amino acids with distinct distributions across the three study groups, although no obvious clustering of NS5B sequences was observed based on HIV co-infection or CD4 cell count. Polymorphisms at amino acid positions associated with resistance to dasabuvir and sofosbuvir were limited, although the Q309R variant associated with ribavirin resistance was present in 12 individuals with HCV mono-infection, 8 HIV/HCV co-infected individuals with CD4 <350 cells/mm3, and 12 HIV/HCV co-infected individuals with CD4 >/=350 cells/mm3. Previously reported fitness altering mutations were rare. CD8+ T cell responses against the human leukocyte antigen (HLA) B57-restricted epitopes NS5B2629-2637 and NS5B2936-2944 are critical for HCV control and were completely conserved in 44 (51.8%) and 70 (82.4%) study participants. These data demonstrate extensive variation across the NS5B gene. Genotypic variation may have a profound impact on HCV replication and pathogenesis and deserves careful evaluation. FAU - Ngwaga, Tshegofatso AU - Ngwaga T AD - Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America. FAU - Kong, Ling AU - Kong L AD - Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America. FAU - Lin, Derrick AU - Lin D AD - Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America. FAU - Schoborg, Cassandra AU - Schoborg C AD - Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America. FAU - Taylor, Lynn E AU - Taylor LE AD - Miriam Hospital and Department of Medicine, Brown University, Providence, Rhode Island, United States of America. FAU - Mayer, Kenneth H AU - Mayer KH AUID- ORCID: 0000-0001-7460-733X AD - Beth Israel Deaconess Medical Center and the Fenway Institute, Boston, Massachusetts, United States of America. FAU - Klein, Robert S AU - Klein RS AD - Hudson Infectious Diseases Associates, Briarcliff Manor, New York, United States of America. FAU - Celentano, David D AU - Celentano DD AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. FAU - Sobel, Jack D AU - Sobel JD AD - Division of Infectious Diseases, School of Medicine, Wayne State University, Detroit, Michigan, United States of America. FAU - Jamieson, Denise J AU - Jamieson DJ AD - Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America. AD - Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia, United States of America. FAU - King, Caroline C AU - King CC AD - Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America. FAU - Tavis, John E AU - Tavis JE AD - Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, United States of America. FAU - Blackard, Jason T AU - Blackard JT AUID- ORCID: 0000-0003-2876-3811 AD - Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America. LA - eng GR - P30 AI060354/AI/NIAID NIH HHS/United States GR - P30 DK078392/DK/NIDDK NIH HHS/United States GR - P30 ES006096/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200804 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antiviral Agents) RN - 0 (RNA, Viral) RN - 0 (Sulfonamides) RN - 0 (Viral Nonstructural Proteins) RN - 56HH86ZVCT (Uracil) RN - CKR7XL41N4 (2-Naphthylamine) RN - DE54EQW8T1 (dasabuvir) RN - EC 2.7.7.48 (NS-5 protein, hepatitis C virus) RN - EC 2.7.7.48 (RNA-Dependent RNA Polymerase) RN - WJ6CA3ZU8B (Sofosbuvir) SB - IM MH - 2-Naphthylamine MH - AIDS-Related Opportunistic Infections/drug therapy/*genetics/virology MH - Adult MH - Amino Acid Sequence MH - Antiviral Agents/therapeutic use MH - CD4 Lymphocyte Count MH - Cohort Studies MH - Coinfection/drug therapy/*genetics/virology MH - Drug Resistance, Viral/genetics MH - Female MH - *Genetic Variation MH - Genotype MH - *HIV MH - Hepacivirus/*genetics MH - Hepatitis C/drug therapy/*genetics/virology MH - Humans MH - Phylogeny MH - RNA, Viral/genetics/isolation & purification MH - RNA-Dependent RNA Polymerase/genetics MH - Sofosbuvir/therapeutic use MH - Sulfonamides/therapeutic use MH - Uracil/analogs & derivatives/therapeutic use MH - Viral Nonstructural Proteins/*genetics PMC - PMC7402467 COIS- JTB is an Academic Editor for PLOS ONE. This does not alter our adherence to PLOS ONE policies on sharing data and materials. EDAT- 2020/08/05 06:00 MHDA- 2020/10/21 06:00 PMCR- 2020/08/04 CRDT- 2020/08/05 06:00 PHST- 2020/05/21 00:00 [received] PHST- 2020/07/20 00:00 [accepted] PHST- 2020/08/05 06:00 [entrez] PHST- 2020/08/05 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] PHST- 2020/08/04 00:00 [pmc-release] AID - PONE-D-20-15298 [pii] AID - 10.1371/journal.pone.0237162 [doi] PST - epublish SO - PLoS One. 2020 Aug 4;15(8):e0237162. doi: 10.1371/journal.pone.0237162. eCollection 2020.