Semen Exosomes Promote Transcriptional Silencing of HIV-1 by Disrupting NF-κB/Sp1/Tat Circuitry

Author:

Welch Jennifer L.1,Kaddour Hussein1,Schlievert Patrick M.1,Stapleton Jack T.123,Okeoma Chioma M.1ORCID

Affiliation:

1. Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

2. Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

3. Medical Service, Iowa City Veterans Affairs Medical Center, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA

Abstract

HIV is most commonly transmitted sexually, and semen is the primary vector. Despite progress in studies of HIV pathogenesis and the success of combination antiretroviral therapy in controlling viral replication, current therapy cannot completely control sexual transmission. Thus, there is a need to identify effective methods of controlling HIV replication and transmission. Recently, it was shown that human semen contains exosomes that protect against HIV infection in vitro . In this study, we identified a mechanism by which semen exosomes inhibited HIV-1 RNA expression. We found that semen exosomes inhibit recruitment of transcription factors NF-κB and Sp1, as well as RNA Pol II, to the promoter region in the 5′ long terminal repeat (LTR) of HIV-1. The HIV-1 early protein transcriptional activator (Tat) was a target of semen exosomes, and semen exosomes inhibited the binding and recruitment of Tat to the HIV-1 LTR.

Funder

HHS | National Institutes of Health

U.S. Department of Veterans Affairs

HHS | NIH | National Institute on Drug Abuse

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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