Immunity
Volume 36, Issue 3, 23 March 2012, Pages 491-501
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Article
Stimulation of HIV-1-Specific Cytolytic T Lymphocytes Facilitates Elimination of Latent Viral Reservoir after Virus Reactivation

https://doi.org/10.1016/j.immuni.2012.01.014Get rights and content
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Summary

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.

Highlights

► Resting CD4+ T cells latently infected with HIV-1 do not die after virus reactivation ► Viral CPEs or patient CTLs do not cause death of HIV-1-infected resting CD4+ T cells ► Stimulated patient CTLs kill infected resting CD4+ T cells after reversal of latency ► Autologous viruses recovered from latent reservoir do not escape from patient CTLs

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