Activation and lysis of human CD4 cells latently infected with HIV-1

Amarendra Pegu, Mangaiarkarasi Asokan, Lan Wu, Keyun Wang, Jason Hataye, Joseph P. Casazza, Xiaoti Guo, Wei Shi, Ivelin Georgiev, Tongqing Zhou, Xuejun Chen, Sijy O'Dell, John Paul Todd, Peter D. Kwong, Srinivas S. Rao, Zhi Yong Yang, Richard A. Koup, John R. Mascola, Gary J. Nabel

Research output: Contribution to journalArticlepeer-review

Abstract

The treatment of AIDS with combination antiretroviral therapy (cART) remains lifelong largely because the virus persists in latent reservoirs. Elimination of latently infected cells could therefore reduce treatment duration and facilitate immune reconstitution. Here we report an approach to reduce the viral reservoir by activating dormant viral gene expression and directing T lymphocytes to lyse previously latent, HIV-1-infected cells. An immunomodulatory protein was created that combines the specificity of a HIV-1 broadly neutralizing antibody with that of an antibody to the CD3 component of the T-cell receptor. CD3 engagement by the protein can stimulate T-cell activation that induces proviral gene expression in latently infected T cells. It further stimulates CD8 T-cell effector function and redirects T cells to lyse these previously latent-infected cells through recognition of newly expressed Env. This immunomodulatory protein could potentially help to eliminate latently infected cells and deplete the viral reservoir in HIV-1-infected individuals.

Original languageEnglish (US)
Article number8447
JournalNature communications
Volume6
DOIs
StatePublished - Oct 20 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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