Stimulation of HIV-1-Specific Cytolytic T Lymphocytes Facilitates Elimination of Latent Viral Reservoir after Virus Reactivation

Liang Shan, Kai Deng, Neeta S. Shroff, Christine M. Durand, S. Alireza Rabi, Hung Chih Yang, Hao Zhang, Joseph B. Margolick, Joel N. Blankson, Robert F. Siliciano

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)491-501
Number of pages11
JournalImmunity
Volume36
Issue number3
DOIs
StatePublished - Mar 23 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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