Work

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

Year: 2019

Type: article

Abstract: 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. Author summaryAlthough antiretroviral therapy (ART) effectively blocks HIV replication, infected people are not cured.As a part of its normal replication cycle, HIV inserts (integrates) a DNA copy of its genome into the genome of infected host cells, which allows the virus to persist as long as the infected cells survive.Not only can these infected cells survive, they can grow and divide, increasing the numbers of infected cells without viral replication.The ability of the infected cells to proliferate plays an important role in maintaining the numbers of infected cells (and the infection) in people on successful therapy.However, there

Source: PLoS Pathogens

DOI: 10.1371/journal.ppat.1007869