Adaptation of an R5 Simian-Human Immunodeficiency Virus Encoding an HIV Clade A Envelope with or without Ablation of Adaptive Host Immunity: Differential Selection of Viral Mutants

Author:

Zhou Mingkui123,Humbert Michael23,Mukhtar Muhammad M.123,Scinto Hanna B.14,Vyas Hemant K.123,Lakhashe Samir K.123,Byrareddy Siddappa N.23,Maurer Gregor15,Thorat Swati23,Owuor Joshua1,Lai Zhao6,Chen Yidong67,Griffiths Anthony1,Chenine Agnès-Laurence2389,Gumber Sanjeev1011,Villinger François1011,Montefiori David12,Ruprecht Ruth M.113234

Affiliation:

1. Texas Biomedical Research Institute, San Antonio, Texas, USA

2. Dana-Farber Cancer Institute, Boston, Massachusetts, USA

3. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA

4. Department of Microbiology, Immunology & Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

5. VetCore, Facility for Research, University of Veterinary Medicine Vienna, Vienna, Austria

6. Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

7. Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

8. Henry M. Jackson Foundation, Bethesda, Maryland, USA

9. Military HIV Research Program, Silver Spring, Maryland, USA

10. Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA

11. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA

12. Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA

13. Southwest National Primate Research Center, San Antonio, Texas, USA

Abstract

In this study, we constructed a simian-human immunodeficiency virus carrying an R5 Kenyan HIV-1 clade A env (SHIV-A). To bypass host immunity, SHIV-A was rapidly passaged in naive macaques or animals depleted of both CD8 + and B cells. Next-generation sequencing identified different mutations that resulted from optimization of viral replicative fitness either in the absence of adaptive immunity or due to pressure from adaptive immune responses.

Funder

HHS | NIH | National Cancer Institute

HHS | National Institutes of Health

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Center for Advancing Translational Sciences

NIH Shared Instrument S10 Grant

Cancer Prevention and Research Institute of Texas

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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