Clonal expansion of SIV-infected cells in macaques on antiretroviral therapy is similar to that of HIV-infected cells in humans

Clonal expansion of HIV infected cells plays an important role in the formation and persistence of the reservoir that allows the virus to persist, in DNA form, despite effective antiretroviral therapy. We used integration site analysis to ask if there is a similar clonal expansion of SIV infected ce...

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Bibliographic Details
Published in:PLoS pathogens 2019-07, Vol.15 (7), p.e1007869
Main Authors: Ferris, Andrea L, Wells, David W, Guo, Shuang, Del Prete, Gregory Q, Swanstrom, Adrienne E, Coffin, John M, Wu, Xiaolin, Lifson, Jeffrey D, Hughes, Stephen H
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
AIDS
Animals
Anti-Retroviral Agents - therapeutic use
Antiretroviral agents
Antiretroviral drugs
Antiretroviral therapy
Biology and life sciences
Biomedical research
Blood
Cancer
CD4-Positive T-Lymphocytes - virology
Cloning
Deoxyribonucleic acid
Disease Reservoirs - virology
DNA
Drug therapy
Expansion
Gene therapy
Genes
Genetic aspects
Genetic research
Highly active antiretroviral therapy
HIV
HIV infections
HIV Infections - drug therapy
HIV Infections - pathology
HIV Infections - virology
HIV patients
Host Microbial Interactions - drug effects
Host Microbial Interactions - genetics
Host Microbial Interactions - physiology
Human immunodeficiency virus
Humans
In Vitro Techniques
Infections
Integration
Laboratories
Lymph nodes
Lymphocytes
Macaca mulatta
Macaques
Medical research
Medicine and Health Sciences
Necropsy
Pathogenesis
Proteins
Research and Analysis Methods
Simian Acquired Immunodeficiency Syndrome - drug therapy
Simian Acquired Immunodeficiency Syndrome - pathology
Simian Acquired Immunodeficiency Syndrome - virology
Simian immunodeficiency virus
Simian Immunodeficiency Virus - pathogenicity
Spleen
Therapy
Viral Load - drug effects
Virus Integration - genetics
Virus Integration - physiology
Virus Replication - drug effects
Viruses
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Summary:Clonal expansion of HIV infected cells plays an important role in the formation and persistence of the reservoir that allows the virus to persist, in DNA form, despite effective antiretroviral therapy. We used integration site analysis to ask if there is a similar clonal expansion of SIV infected cells in macaques. We show that the distribution of HIV and SIV integration sites in vitro is similar and that both viruses preferentially integrate in many of the same genes. We obtained approximately 8000 integration sites from blood samples taken from SIV-infected macaques prior to the initiation of ART, and from blood, spleen, and lymph node samples taken at necropsy. Seven clones were identified in the pre-ART samples; one persisted for a year on ART. An additional 100 clones were found only in on-ART samples; a number of these clones were found in more than one tissue. The timing and extent of clonal expansion of SIV-infected cells in macaques and HIV-infected cells in humans is quite similar. This suggests that SIV-infected macaques represent a useful model of the clonal expansion of HIV infected cells in humans that can be used to evaluate strategies intended to control or eradicate the viral reservoir.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1007869