title: Asymmetric division of activated latently infected cells may explain the decay kinetics of the HIV-1 latent reservoir and intermittent viral blips.
abstract: Most HIV-infected patients when treated with combination antiretroviral therapy achieve viral loads that are below the current limit of detection of standard assays after a few months. Despite this, virus eradication from the host has not been achieved. Latent, replication-competent HIV-1 can generally be identified in resting memory CD4(+) T cells in patients with "undetectable" viral loads. Turnover of these cells is extremely slow but virus can be released from the latent reservoir quickly upon cessation of therapy. In addition, a number of patients experience transient episodes of viremia, or HIV-1 blips, even with suppression of the viral load to below the limit of detection for many years. The mechanisms underlying the slow decay of the latent reservoir and the occurrence of intermittent viral blips have not been fully elucidated. In this study, we address these two issues by developing a mathematical model that explores a hypothesis about latently infected cell activation. We propose that asymmetric division of latently infected cells upon sporadic antigen encounter may both replenish the latent reservoir and generate intermittent viral blips. Interestingly, we show that occasional replenishment of the latent reservoir induced by reactivation of latently infected cells may reconcile the differences between the divergent estimates of the half-life of the latent reservoir in the literature.
authors.affiliation: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: Libin
authors.initials: L
authors.lastname: Rong
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003198:Computer Simulation; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D019562:Viral Load; D017735:Virus Latency