About this item:

79 Views | 41 Downloads

Author Notes:

Correspondence: jason.blackard@uc.edu

Author contributions: Tshegofatso Ngwaga: Data curation, Formal analysis, Writing – review & editing. Ling Kong: Formal analysis, Investigation, Writing – review & editing. Derrick Lin: Formal analysis, Writing – review & editing. Cassandra Schoborg: Formal analysis, Writing – review & editing.

Lynn E. Taylor: Conceptualization, Methodology, Project administration, Writing – review & editing. Kenneth H. Mayer: Conceptualization, Methodology, Project administration, Writing – review & editing. Robert S. Klein: Conceptualization, Methodology, Project administration, Writing – review & editing. David D. Celentano: Conceptualization, Methodology, Project administration, Writing – review & editing.

Jack D. Sobel: Conceptualization, Methodology, Project administration, Writing – review & editing. Denise J. Jamieson: Conceptualization, Methodology, Project administration, Writing – review & editing. Caroline C. King: Data curation, Project administration, Writing – review & editing.

John E. Tavis: Conceptualization, Methodology, Project administration, Writing – review & editing. and Jason T. Blackard: Conceptualization, Formal analysis, Funding acquisition, Project administration, Supervision, Writing – original draft, Writing – review & editing.

The authors would like to thank the HER Study staff and participants. The HER Study group consists of Robert S. Klein, MD, Ellie Schoenbaum, MD, Julia Arnsten, MD, MPH, Robert D. Burk, MD, Chee Jen Chang, PhD, Penelope Demas, PhD, and Andrea Howard, MD, MSc, from Montefiore Medical Center and the Albert Einstein College of Medicine;

Jack Sobel, MD, Suzanne Ohmit, DrPH, William Brown PhD, Michael Long PhD, Wayne Lancaster PhD, and Jose Vazquez, MD, from the Wayne State University School of Medicine; Anne Rompalo, MD, David Vlahov, PhD and David Celentano, PhD, from the Johns Hopkins University School of Medicine;

Charles Carpenter, MD, Kenneth Mayer, MD, Susan Cu-Uvin, MD, Timothy Flanigan, MD, Joseph Hogan, ScD, Valerie Stone, MD, Karen Tashima, MD, and Josiah Rich, MD from the Brown University School of Medicine; Ann Duerr, MD, PhD, Lytt I. Gardner, PhD, Chad Heilig, PhD, Scott D. Holmberg, MD, Caroline C. King, PhD

Denise J. Jamieson, MD, MPH, Janet S. Moore, PhD, Ruby M. Phelps, BS, Dawn K. Smith, MD, MPH and Dora Warren, PhD from the Centers for Disease Control and Prevention; and Katherine Davenny, MPH from the National Institute of Drug Abuse.

Disclosures: JTB is an Academic Editor for PLOS ONE. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Subjects:

Research Funding:

This work was funded by the National Institute of General Medical Sciences (award GM105414 to JTB).

Amplicon-seq was conducted by the Genomics, Epigenomics and Sequencing Core at the Department of Environmental Health within University of Cincinnati College of Medicine and is supported in part by NIEHS P30 ES006096).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • Human immunodeficiency virus (HIV)
  • Hypervariable region 1
  • Dependent rma polynase
  • Compensatory mutations
  • Secondary structures
  • Liver damage
  • Resistance
  • Genotype
  • Identification
  • Infection

Diversity of the hepatitis C virus NS5B gene during HIV co-infection

Show all authors Show less authors

Tools:

Journal Title:

PLOS ONE

Volume:

Volume 15, Number 8

Publisher:

, Pages e0237162-e0237162

Type of Work:

Article | Final Publisher PDF

Abstract:

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 monoinfection, antiretroviral (ART)-naïve women with HIV/HCV co-infection and CD4 cell count <350 cells/mm3, and ART-naïve 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.

Copyright information:

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

This is an Open Access work distributed under the terms of the Creative Commons Universal : Public Domain Dedication License (https://creativecommons.org/publicdomain/zero/1.0/).
Export to EndNote