Stimulation of HIV-1-Specific Cytolytic T Lymphocytes Facilitates Elimination of Latent Viral Reservoir after Virus Reactivation
Journal
Immunity
Journal Volume
36
Journal Issue
3
Pages
491-501
Date Issued
2012
Author(s)
Shan L
Deng K
Shroff N.S
Durand C.M
Rabi S.A
Zhang H
Margolick J.B
Blankson J.N
Siliciano R.F.
Abstract
Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication but cannot eliminate the virus because HIV-1 establishes latent infection. Interruption of HAART leads to a rapid rebound of viremia, so life-long treatment is required. Efforts to purge the latent reservoir have focused on reactivating latent proviruses without inducing global T cell activation. However, the killing of the infected cells after virus reactivation, which is essential for elimination of the reservoir, has not been assessed. Here we show that after reversal of latency in an in vitro model, infected resting CD4 + T cells survived despite viral cytopathic effects, even in the presence of autologous cytolytic T lymphocytes (CTLs) from most patients on HAART. Antigen-specific stimulation of patient CTLs led to efficient killing of infected cells. These results demonstrate that stimulating HIV-1-specific CTLs prior to reactivating latent HIV-1 may be essential for successful eradication efforts and should be considered in future clinical trials. ? 2012 Elsevier Inc..
SDGs
Other Subjects
antiretrovirus agent; article; CD4+ T lymphocyte; CD8+ T lymphocyte; cell killing; cell proliferation; controlled study; cytotoxic T lymphocyte; disease carrier; highly active antiretroviral therapy; human; human cell; Human immunodeficiency virus 1; immunostimulation; in vitro study; priority journal; T lymphocyte activation; virus latency; virus reactivation; Antiretroviral Therapy, Highly Active; CD4-Positive T-Lymphocytes; Coculture Techniques; Cytopathogenic Effect, Viral; Cytotoxicity, Immunologic; HIV Infections; HIV-1; Humans; Lymphocyte Activation; Proviruses; T-Lymphocytes, Cytotoxic; Virus Latency; Virus Replication
Type
journal article