Latency reversal plus natural killer cells diminish HIV reservoir in vivo

Jocelyn T. Kim (), Tian-Hao Zhang, Camille Carmona, Bryanna Lee, Christopher S. Seet, Matthew Kostelny, Nisarg Shah, Hongying Chen, Kylie Farrell, Mohamed S. A. Soliman, Melanie Dimapasoc, Michelle Sinani, Kenia Yazmin Reyna Blanco, David Bojorquez, Hong Jiang, Yuan Shi, Yushen Du, Natalia L. Komarova, Dominik Wodarz, Paul A. Wender, Matthew D. Marsden, Ren Sun and Jerome A. Zack
Additional contact information
Jocelyn T. Kim: University of California Los Angeles
Tian-Hao Zhang: University of California Los Angeles
Camille Carmona: University of California Los Angeles
Bryanna Lee: University of California Los Angeles
Christopher S. Seet: University of California Los Angeles
Matthew Kostelny: University of California Los Angeles
Nisarg Shah: University of California Los Angeles
Hongying Chen: University of California Los Angeles
Kylie Farrell: University of California Los Angeles
Mohamed S. A. Soliman: University of California Los Angeles
Melanie Dimapasoc: University of California Los Angeles
Michelle Sinani: University of California Los Angeles
Kenia Yazmin Reyna Blanco: University of California Los Angeles
David Bojorquez: University of California Los Angeles
Hong Jiang: University of California
Yuan Shi: University of California
Yushen Du: University of California
Natalia L. Komarova: University of California, Irvine
Dominik Wodarz: University of California, Irvine
Paul A. Wender: Stanford University
Matthew D. Marsden: University of California, Irvine
Ren Sun: University of California
Jerome A. Zack: University of California Los Angeles

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract HIV is difficult to eradicate due to the persistence of a long-lived reservoir of latently infected cells. Previous studies have shown that natural killer cells are important to inhibiting HIV infection, but it is unclear whether the administration of natural killer cells can reduce rebound viremia when anti-retroviral therapy is discontinued. Here we show the administration of allogeneic human peripheral blood natural killer cells delays viral rebound following interruption of anti-retroviral therapy in humanized mice infected with HIV-1. Utilizing genetically barcoded virus technology, we show these natural killer cells efficiently reduced viral clones rebounding from latency. Moreover, a kick and kill strategy comprised of the protein kinase C modulator and latency reversing agent SUW133 and allogeneic human peripheral blood natural killer cells during anti-retroviral therapy eliminated the viral reservoir in a subset of mice. Therefore, combinations utilizing latency reversal agents with targeted cellular killing agents may be an effective approach to eradicating the viral reservoir.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27647-0

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DOI: 10.1038/s41467-021-27647-0

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