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 () and Gary J. Nabel ()
Additional contact information
Amarendra Pegu: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Mangaiarkarasi Asokan: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Lan Wu: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Keyun Wang: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Jason Hataye: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Joseph P. Casazza: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Xiaoti Guo: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Wei Shi: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Ivelin Georgiev: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Tongqing Zhou: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Xuejun Chen: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Sijy O’Dell: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
John-Paul Todd: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Peter D. Kwong: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Srinivas S. Rao: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Zhi-yong Yang: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Richard A. Koup: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
John R. Mascola: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health
Gary J. Nabel: Vaccine Research Center National Institute for Allergy and Infectious Diseases, National Institutes of Health

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9447

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