TY - JOUR
T1 - Clearance of HIV infection by selective elimination of host cells capable of producing HIV
AU - Li, Min
AU - Liu, Wei
AU - Bauch, Tonya
AU - Graviss, Edward A.
AU - Arduino, Roberto C.
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).
PY - 2020/8/13
Y1 - 2020/8/13
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.
AB - 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.
KW - Animals
KW - Antigens, CD34/metabolism
KW - Apoptosis/drug effects
KW - Autophagy/physiology
KW - Azepines/pharmacology
KW - CD4-Positive T-Lymphocytes/metabolism
KW - HIV Infections/prevention & control
KW - HIV-1/pathogenicity
KW - Humans
KW - Mice
KW - Organophosphates/pharmacology
KW - Piperazines/pharmacology
KW - Pyridines/pharmacology
KW - Pyrimidinones/pharmacology
KW - RNA, Viral/metabolism
KW - T-Lymphocytes/drug effects
KW - Triazoles/pharmacology
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UR - http://www.scopus.com/inward/citedby.url?scp=85089394223&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-17753-w
DO - 10.1038/s41467-020-17753-w
M3 - Article
C2 - 32792548
AN - SCOPUS:85089394223
SN - 2041-1723
VL - 11
SP - 4051
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4051
ER -