Heightened resistance to host type 1 interferons characterizes HIV-1 at transmission and after antiretroviral therapy interruption

Marcos V. P. Gondim; Scott Sherrill-Mix; Frederic Bibollet-Ruche; Ronnie M. Russell; Stephanie Trimboli; Andrew G. Smith; Yingying Li; Weimin Liu; Alexa N. Avitto; Julia C. DeVoto; Jesse Connell; Angharad E. Fenton-May; Pierre Pellegrino; Ian Williams; Emmanouil Papasavvas; Julio C. C. Lorenzi; D. Brenda Salantes; Felicity Mampe; M. Alexandra Monroy; Yehuda Z. Cohen; Sonya Heath; Michael S. Saag; Luis J. Montaner; Ronald G. Collman; Janet M. Siliciano; Robert F. Siliciano; Lindsey J. Plenderleith; Paul M. Sharp; Marina Caskey; Michel C. Nussenzweig; George M. Shaw; Persephone Borrow; Katharine J. Bar; Beatrice H. Hahn

doi:10.1126/scitranslmed.abd8179

Research ArticleHIV

Heightened resistance to host type 1 interferons characterizes HIV-1 at transmission and after antiretroviral therapy interruption

View ORCID ProfileMarcos V. P. Gondim¹,*,†,
View ORCID ProfileScott Sherrill-Mix ¹,²,*,
Frederic Bibollet-Ruche¹,²,
View ORCID ProfileRonnie M. Russell¹,²,
Stephanie Trimboli³,
Andrew G. Smith⁴,
Yingying Li¹,
Weimin Liu¹,
View ORCID ProfileAlexa N. Avitto⁵,
Julia C. DeVoto⁶,
View ORCID ProfileJesse Connell¹,²,
View ORCID ProfileAngharad E. Fenton-May⁷,
Pierre Pellegrino⁸,
View ORCID ProfileIan Williams⁸,
Emmanouil Papasavvas⁹,
View ORCID ProfileJulio C. C. Lorenzi¹⁰,
View ORCID ProfileD. Brenda Salantes¹¹,
Felicity Mampe¹,
M. Alexandra Monroy¹,
View ORCID ProfileYehuda Z. Cohen¹²,
View ORCID ProfileSonya Heath¹³,
View ORCID ProfileMichael S. Saag ¹³,
View ORCID ProfileLuis J. Montaner ⁹,
View ORCID ProfileRonald G. Collman ¹,²,
View ORCID ProfileJanet M. Siliciano¹⁴,
View ORCID ProfileRobert F. Siliciano¹⁴,¹⁵,
Lindsey J. Plenderleith¹⁶,¹⁷,
Paul M. Sharp¹⁶,¹⁷,
View ORCID ProfileMarina Caskey ¹⁰,
View ORCID ProfileMichel C. Nussenzweig ¹⁰,¹⁸,
View ORCID ProfileGeorge M. Shaw¹,²,
View ORCID ProfilePersephone Borrow ⁷,
View ORCID ProfileKatharine J. Bar¹,² and
View ORCID ProfileBeatrice H. Hahn ¹,²,‡

¹Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
²Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
³University of Massachusetts Medical School, Worcester, MA 01655, USA.
⁴WuXi AppTec Inc., Philadelphia, PA 19112, USA.
⁵Gene Therapy Program, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁶Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.
⁷Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7FZ, UK.
⁸Centre for Clinical Research in Infection and Sexual Health, Institute for Global Health, University College London, London WC1E 6JB, UK.
⁹Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA.
¹⁰Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.
¹¹Century Therapeutics, Philadelphia, PA 19104, USA.
¹²Sanofi, Bridgewater, NJ 08807, USA.
¹³Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
¹⁴Department of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
¹⁵Howard Hughes Medical Institute, Johns Hopkins University, Baltimore, MD 21205, USA.
¹⁶Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3FL, UK.
¹⁷Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3FL, UK.
¹⁸Howard Hughes Medical Institute, Rockefeller University, New York, NY 10065, USA.

↵‡Corresponding author. Email: bhahn{at}pennmedicine.upenn.edu

↵* These authors contributed equally to this work.
↵† Present address: Bristol Myers Squibb, 556 Morris Avenue, Summit, NJ 07901, USA.

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Science Translational Medicine 13 Jan 2021:
Vol. 13, Issue 576, eabd8179
DOI: 10.1126/scitranslmed.abd8179

Marcos V. P. Gondim

1Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Scott Sherrill-Mix

1Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

2Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Frederic Bibollet-Ruche

1Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

2Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Ronnie M. Russell

1Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

2Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Stephanie Trimboli

3University of Massachusetts Medical School, Worcester, MA 01655, USA.

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Andrew G. Smith

4WuXi AppTec Inc., Philadelphia, PA 19112, USA.

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Yingying Li

1Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Weimin Liu

1Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Alexa N. Avitto

5Gene Therapy Program, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Julia C. DeVoto

6Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.

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Jesse Connell

1Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

2Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Angharad E. Fenton-May

7Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7FZ, UK.

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Pierre Pellegrino

8Centre for Clinical Research in Infection and Sexual Health, Institute for Global Health, University College London, London WC1E 6JB, UK.

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Ian Williams

8Centre for Clinical Research in Infection and Sexual Health, Institute for Global Health, University College London, London WC1E 6JB, UK.

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Emmanouil Papasavvas

9Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA.

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Julio C. C. Lorenzi

10Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.

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D. Brenda Salantes

11Century Therapeutics, Philadelphia, PA 19104, USA.

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Felicity Mampe

1Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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M. Alexandra Monroy

1Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Yehuda Z. Cohen

12Sanofi, Bridgewater, NJ 08807, USA.

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Sonya Heath

13Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

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Michael S. Saag

13Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

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Luis J. Montaner

9Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA.

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Ronald G. Collman

1Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

2Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Janet M. Siliciano

14Department of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.

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Robert F. Siliciano

14Department of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.

15Howard Hughes Medical Institute, Johns Hopkins University, Baltimore, MD 21205, USA.

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Lindsey J. Plenderleith

16Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3FL, UK.

17Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3FL, UK.

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Paul M. Sharp

16Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3FL, UK.

17Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3FL, UK.

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Marina Caskey

10Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.

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Michel C. Nussenzweig

10Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.

18Howard Hughes Medical Institute, Rockefeller University, New York, NY 10065, USA.

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George M. Shaw

1Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

2Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Persephone Borrow

7Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7FZ, UK.

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Katharine J. Bar

1Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

2Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Beatrice H. Hahn

1Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

2Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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For correspondence: bhahn@pennmedicine.upenn.edu

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Putting pressure on HIV

Type 1 interferons provide early host immune defense against viruses, including HIV-1, by promoting expression of proteins that have direct or indirect antiviral activity. It remains unclear how viruses that persist long term, such as HIV-1, escape type 1 interferon–mediated pressure. Gondim et al. characterize interferon resistance in HIV-1 isolates acquired from HIV-1–infected individuals over several years. The authors found that HIV-1 isolates acquired at the time of initial infection or during interruption of antiretroviral therapy were the most resistant to type 1 interferons. These findings underpin the importance of type 1 interferons in controlling HIV-1 infection in the host.

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Heightened resistance to host type 1 interferons characterizes HIV-1 at transmission and after antiretroviral therapy interruption

Putting pressure on HIV

Science Translational Medicine

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