Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistence

Journal Article · 09 July 2018 · Proceedings of the National Academy of Sciences of the United States of America

DOI: https://doi.org/10.1073/pnas.1805267115 · OSTI ID:1459484

Ke, Ruian ^[1]; Li, Hui ^[2]; Wang, Shuyi ^[2]; Ding, Wenge ^[2]; Ribeiro, Ruy M.  ^[3]; Giorgi, Elena E. ^[4]; Bhattacharya, Tanmoy  ^[5]; Barnard, Richard J. O. ^[6]; Hahn, Beatrice H. ^[2]; Shaw, George M. ^[2]; Perelson, Alan S. ^[7]

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1. Department of Mathematics, North Carolina State University, Raleigh, NC 27695,, Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545,
2. Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104,, Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104,
3. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545,, Laboratory of Biomathematics, Faculty of Medicine, University of Lisbon, 1600-276 Lisbon, Portugal,
4. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545,
5. Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545,, Santa Fe Institute, Santa Fe, NM 87501,
6. Department of Infectious Disease, Merck &, Co., Inc., Kenilworth, NJ 07033
7. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545,, Santa Fe Institute, Santa Fe, NM 87501,

Significance Viral populations exhibit an extraordinary ability to survive abrupt changes in host environment by rapidly generating adaptive mutations. However, our understanding of how viral populations respond to selection pressure and the underlying molecular mechanisms supporting viral adaptation in vivo is limited. Here, we report a set of clinical data sampled from subjects chronically infected by hepatitis C virus (HCV). The data show rapid expansion and turnover of drug-resistant viruses following treatment with an HCV protease inhibitor. By fitting mathematical models to the data, we propose that superinfection and cure of infected cells play critical roles in facilitating the rapid expansion and turnover of viral populations. Our results highlight the importance of considering intracellular viral competition in understanding rapid viral adaptation.

• Sponsoring Organization: USDOE
• Grant/Contract Number: AC52-06NA25396
• OSTI ID: 1459484
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 30 Vol. 115; ISSN 0027-8424
• Publisher: Proceedings of the National Academy of SciencesCopyright Statement
• Country of Publication: United States
• Language: English