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.

Autor:	Zhou M; Texas Biomedical Research Institute, San Antonio, Texas, USA.; Dana-Farber Cancer Institute, Boston, Massachusetts, USA.; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA., Humbert M; Dana-Farber Cancer Institute, Boston, Massachusetts, USA.; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA., Mukhtar MM; Texas Biomedical Research Institute, San Antonio, Texas, USA.; Dana-Farber Cancer Institute, Boston, Massachusetts, USA.; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA., Scinto HB; Texas Biomedical Research Institute, San Antonio, Texas, USA.; Department of Microbiology, Immunology & Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Vyas HK; Texas Biomedical Research Institute, San Antonio, Texas, USA.; Dana-Farber Cancer Institute, Boston, Massachusetts, USA.; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA., Lakhashe SK; Texas Biomedical Research Institute, San Antonio, Texas, USA.; Dana-Farber Cancer Institute, Boston, Massachusetts, USA.; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA., Byrareddy SN; Dana-Farber Cancer Institute, Boston, Massachusetts, USA.; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA., Maurer G; Texas Biomedical Research Institute, San Antonio, Texas, USA.; VetCore, Facility for Research, University of Veterinary Medicine Vienna, Vienna, Austria., Thorat S; Dana-Farber Cancer Institute, Boston, Massachusetts, USA.; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA., Owuor J; Texas Biomedical Research Institute, San Antonio, Texas, USA., Lai Z; Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Chen Y; Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.; Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA., Griffiths A; Texas Biomedical Research Institute, San Antonio, Texas, USA., Chenine AL; Dana-Farber Cancer Institute, Boston, Massachusetts, USA.; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.; Henry M. Jackson Foundation, Bethesda, Maryland, USA.; Military HIV Research Program, Silver Spring, Maryland, USA., Gumber S; Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA., Villinger F; Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA., Montefiori D; Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA., Ruprecht RM; Texas Biomedical Research Institute, San Antonio, Texas, USA rruprecht@txbiomed.org.; Southwest National Primate Research Center, San Antonio, Texas, USA.; Dana-Farber Cancer Institute, Boston, Massachusetts, USA.; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.; Department of Microbiology, Immunology & Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2019 Apr 17; Vol. 93 (9). Date of Electronic Publication: 2019 Apr 17 (Print Publication: 2019).
DOI:	10.1128/JVI.02267-18
Abstrakt:	Simian-human immunodeficiency virus (SHIV) infection in rhesus macaques (RMs) resembles human immunodeficiency virus type 1 (HIV-1) infection in humans and serves as a tool to evaluate candidate AIDS vaccines. HIV-1 clade A (HIV-A) predominates in parts of Africa. We constructed an R5 clade A SHIV (SHIV-A; strain SHIV-KNH1144) carrying env from a Kenyan HIV-A. SHIV-A underwent rapid serial passage through six RMs. To allow unbridled replication without adaptive immunity, we simultaneously ablated CD8 + and B cells with cytotoxic monoclonal antibodies in the next RM, resulting in extremely high viremia and CD4 + T-cell loss. Infected blood was then transferred into two non-immune-depleted RMs, where progeny SHIV-A showed increased replicative capacity and caused AIDS. We reisolated SHIV-KNH1144p4, which was replication competent in peripheral blood mononuclear cells (PBMC) of all RMs tested. Next-generation sequencing of early- and late-passage SHIV-A strains identified mutations that arose due to "fitness" virus optimization in the former and mutations exhibiting signatures typical for adaptive host immunity in the latter. "Fitness" mutations are best described as mutations that allow for better fit of the HIV-A Env with SIV-derived virion building blocks or host proteins and mutations in noncoding regions that accelerate virus replication, all of which result in the outgrowth of virus variants in the absence of adaptive T-cell and antibody-mediated host immunity. IMPORTANCE 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. (Copyright © 2019 American Society for Microbiology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu