Journal Article

Latency reversal plus natural killer cells diminish HIV reservoir in vivo

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

2022

نظرة عامة

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. Here, Kim et al. describe a new kick and kill strategy utilizing a single administration of a protein kinase C modulator and latency reversing agent in combination with injections of allogeneic peripheral blood natural killer cells diminishes the HIV reservoir in HIV-infected humanized mice.

• الناشر: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• موضوع: 13/106 / 13/31 / 38/22 / 38/88 / 42 / 45 / 45/77 / 49/91 / 631/250/255/1901 / 631/326/596/2564 / Animals / Anti-HIV Agents - pharmacology / Antiretroviral drugs / Blood / Bone Marrow - drug effects / Bone Marrow - immunology / Bone Marrow - virology / CD4-Positive T-Lymphocytes - drug effects / CD4-Positive T-Lymphocytes - immunology / CD4-Positive T-Lymphocytes - virology / Coculture Techniques / Female / HIV / HIV Infections - genetics / HIV Infections - immunology / HIV Infections - therapy / HIV Infections - virology / HIV-1 - drug effects / HIV-1 - genetics / HIV-1 - immunology / Host-Pathogen Interactions - drug effects / Host-Pathogen Interactions - genetics / Host-Pathogen Interactions - immunology / Human immunodeficiency virus / Humanities and Social Sciences / Humans / Killer Cells, Natural - immunology / Killer Cells, Natural - transplantation / Kinases / Latency / Latent infection / Male / Mice / Mice, Transgenic / multidisciplinary / Natural killer cells / Peripheral blood / Protein kinase C / Protein Kinase C - genetics / Protein Kinase C - immunology / Protein Kinase Inhibitors - pharmacology / Proteins / Science / Science (multidisciplinary) / Spleen - drug effects / Spleen - immunology / Spleen - virology / Therapy / Viral Load - drug effects / Viremia / Viremia - genetics / Viremia - immunology / Viremia - therapy / Viremia - virology / Virus Latency - drug effects / Virus Replication - drug effects