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Activation and lysis of human CD4 cells latently infected with HIV-1
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Activation and lysis of human CD4 cells latently infected with HIV-1
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Journal Article
Activation and lysis of human CD4 cells latently infected with HIV-1
2015
Overview
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.
The elimination of latently infected cells is a sought after goal in the treatment of HIV-1 infections. Here the authors develop an approach to eliminate latently HIV-1 infected cells by using an immunomodulatory protein, which can activate viral gene expression in these cells and direct T lymphocytes to lyse them
in vitro
.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Pub. Group
Subject
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/ 38/90
/ 692/308
/ 82/16
/ 82/29
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/ Animals
/ Antibodies, Neutralizing - pharmacology
/ CD4-Positive T-Lymphocytes - drug effects
/ CD4-Positive T-Lymphocytes - virology
/ CD8-Positive T-Lymphocytes - drug effects
/ CD8-Positive T-Lymphocytes - immunology
/ env Gene Products, Human Immunodeficiency Virus - immunology
/ Gene Expression Regulation, Viral - drug effects
/ HIV Infections - drug therapy
/ Humanities and Social Sciences
/ Humans
/ Immunologic Factors - pharmacology
/ Lymphocyte Activation - drug effects
/ Lymphocyte Activation - immunology
/ Real-Time Polymerase Chain Reaction
/ Science
