Clearance of HIV infection by selective elimination of host cells capable of producing HIV

Min Li; Wei Liu; Tonya Bauch; Edward A. Graviss; Roberto C. Arduino; Jason T. Kimata; Min Chen; Jin Wang

doi:10.1038/s41467-020-17753-w

Clearance of HIV infection by selective elimination of host cells capable of producing HIV

Min Li, Wei Liu, Tonya Bauch, Edward A. Graviss, Roberto C. Arduino, Jason T. Kimata, Min Chen, Jin Wang

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

The RNA genome of the human immunodeficiency virus (HIV) is reverse-transcribed into DNA and integrated into the host genome, resulting in latent infections that are difficult to clear. Here we show an approach to eradicate HIV infections by selective elimination of host cells harboring replication-competent HIV (SECH), which includes viral reactivation, induction of cell death, inhibition of autophagy and the blocking of new infections. Viral reactivation triggers cell death specifically in HIV-1-infected T cells, which is promoted by agents that induce apoptosis and inhibit autophagy. SECH treatments can clear HIV-1 in >50% mice reconstituted with a human immune system, as demonstrated by the lack of viral rebound after withdrawal of treatments, and by adoptive transfer of treated lymphocytes into uninfected humanized mice. Moreover, SECH clears HIV-1 in blood samples from HIV-1-infected patients. Our results suggest a strategy to eradicate HIV infections by selectively eliminating host cells capable of producing HIV.

Original language	English (US)
Article number	4051
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-17753-w
State	Published - Aug 13 2020

ASJC Scopus subject areas

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

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title = "Clearance of HIV infection by selective elimination of host cells capable of producing HIV",

abstract = "The RNA genome of the human immunodeficiency virus (HIV) is reverse-transcribed into DNA and integrated into the host genome, resulting in latent infections that are difficult to clear. Here we show an approach to eradicate HIV infections by selective elimination of host cells harboring replication-competent HIV (SECH), which includes viral reactivation, induction of cell death, inhibition of autophagy and the blocking of new infections. Viral reactivation triggers cell death specifically in HIV-1-infected T cells, which is promoted by agents that induce apoptosis and inhibit autophagy. SECH treatments can clear HIV-1 in >50% mice reconstituted with a human immune system, as demonstrated by the lack of viral rebound after withdrawal of treatments, and by adoptive transfer of treated lymphocytes into uninfected humanized mice. Moreover, SECH clears HIV-1 in blood samples from HIV-1-infected patients. Our results suggest a strategy to eradicate HIV infections by selectively eliminating host cells capable of producing HIV.",

author = "Min Li and Wei Liu and Tonya Bauch and Graviss, {Edward A.} and Arduino, {Roberto C.} and Kimata, {Jason T.} and Min Chen and Jin Wang",

note = "Funding Information: We thank Albert Jang, Srikanth Kodali, Le Kuai, Wayne Marasco, and Jun-Zheng Wang for technical support, and Andrew Rice for discussions. We thank Laurie Minze and Olga Ortiz for administrative support, and the Houston Methodist Research Institute Bior-epository for providing patient samples. This study was supported by funding from the NIH (R01AI116644 and R01AI123221 to J.W., R33AI116167 to J.T.K., 5P30AI036211 to R.C.A.), the Cancer Prevention and Research Institute of Texas (RP160384 to J.W. and M.C.), the US Department of Defense (PR140593 to M.C.), and the Houston Methodist Research Institute (to J.W.). Publisher Copyright: {\textcopyright} 2020, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

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AU - Li, Min

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AU - Kimata, Jason T.

AU - Chen, Min

AU - Wang, Jin

N1 - Funding Information: We thank Albert Jang, Srikanth Kodali, Le Kuai, Wayne Marasco, and Jun-Zheng Wang for technical support, and Andrew Rice for discussions. We thank Laurie Minze and Olga Ortiz for administrative support, and the Houston Methodist Research Institute Bior-epository for providing patient samples. This study was supported by funding from the NIH (R01AI116644 and R01AI123221 to J.W., R33AI116167 to J.T.K., 5P30AI036211 to R.C.A.), the Cancer Prevention and Research Institute of Texas (RP160384 to J.W. and M.C.), the US Department of Defense (PR140593 to M.C.), and the Houston Methodist Research Institute (to J.W.). Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

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N2 - The RNA genome of the human immunodeficiency virus (HIV) is reverse-transcribed into DNA and integrated into the host genome, resulting in latent infections that are difficult to clear. Here we show an approach to eradicate HIV infections by selective elimination of host cells harboring replication-competent HIV (SECH), which includes viral reactivation, induction of cell death, inhibition of autophagy and the blocking of new infections. Viral reactivation triggers cell death specifically in HIV-1-infected T cells, which is promoted by agents that induce apoptosis and inhibit autophagy. SECH treatments can clear HIV-1 in >50% mice reconstituted with a human immune system, as demonstrated by the lack of viral rebound after withdrawal of treatments, and by adoptive transfer of treated lymphocytes into uninfected humanized mice. Moreover, SECH clears HIV-1 in blood samples from HIV-1-infected patients. Our results suggest a strategy to eradicate HIV infections by selectively eliminating host cells capable of producing HIV.

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Clearance of HIV infection by selective elimination of host cells capable of producing HIV

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