2020年1月22日，《自然》杂志在线发表了美国北卡罗莱纳大学教堂山分校J. Victor Garcia研究小组的最新成果。他们指出，通过体内非经典的NF-κB信号能够逆转全身性HIV和SIV潜伏期。

Title: Systemic HIV and SIV latency reversal via non-canonical NF-κB signalling in vivo

Author: Christopher C. Nixon, Maud Mavigner, Gavin C. Sampey, Alyssa D. Brooks, Rae Ann Spagnuolo, David M. Irlbeck, Cameron Mattingly, Phong T. Ho, Nils Schoof, Corinne G. Cammon, Greg K. Tharp, Matthew Kanke, Zhang Wang, Rachel A. Cleary, Amit A. Upadhyay, Chandrav De, Saintedym R. Wills, Shane D. Falcinelli, Cristin Galardi, Hasse Walum, Nathaniel J. Schramm, Jennifer Deutsch, Jeffrey D. Lifson, Christine M. Fennessey, Brandon F. Keele, Sherrie Jean, Sean Maguire, Baolin Liao, Edward P. Browne, Robert G. Ferris, Jessica H. Brehm, David Favre, Thomas H. Vanderford, Steven E. Bosinger, Corbin D. Jones, Jean-Pierre Routy, Nancie M. Archin, David M. Margolis, Angela Wahl, Richard M. Dunham, Guido Silvestri, Ann Chahroudi, J. Victor Garcia

Issue&Volume: 2020-01-22

Abstract: 

Long-lasting, latently infected resting CD4+ T cells are the greatest obstacle to obtaining a cure for HIV infection, as these cells can persist despite decades of treatment with antiretroviral therapy (ART). Estimates indicate that more than 70 years of continuous, fully suppressive ART are needed to eliminate the HIV reservoir1. Alternatively, induction of HIV from its latent state could accelerate the decrease in the reservoir, thus reducing the time to eradication. Previous attempts to reactivate latent HIV in preclinical animal models and in clinical trials have measured HIV induction in the peripheral blood with minimal focus on tissue reservoirs and have had limited effect2,3,4,5,6,7,8,9. Here we show that activation of the non-canonical NF-κB signalling pathway by AZD5582 results in the induction of HIV and SIV RNA expression in the blood and tissues of ART-suppressed bone-marrow–liver–thymus (BLT) humanized mice and rhesus macaques infected with HIV and SIV, respectively. Analysis of resting CD4+ T cells from tissues after AZD5582 treatment revealed increased SIV RNA expression in the lymph nodes of macaques and robust induction of HIV in almost all tissues analysed in humanized mice, including the lymph nodes, thymus, bone marrow, liver and lung. This promising approach to latency reversal—in combination with appropriate tools for systemic clearance of persistent HIV infection—greatly increases opportunities for HIV eradication.

DOI: 10.1038/s41586-020-1951-3

Source: https://www.nature.com/articles/s41586-020-1951-3