Human galectin-9 promotes the expansion of HIV reservoirs in vivo in humanized mice

• Published in: AIDS (London) Vol. 37; no. 4; pp. 571 - 577
• Main Authors: Yuan, Zhe, Giron, Leila B, Hart, Colin, Gyampoh, Akwasi, Koshy, Jane, Hong, Kai Ying, Niki, Toshiro, Premeaux, Thomas A, Ndhlovu, Lishomwa C, Deleage, Claire, Montaner, Luis J, Abdel-Mohsen, Mohamed
• Format: Journal Article
• Language: English
• Published: England 15.03.2023
• Subjects: Animals; CD4-Positive T-Lymphocytes; Galectins; HIV Infections; HIV-1 - genetics; Humans; Inflammation; Mice; RNA
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0000000000003443

The human endogenous protein galectin-9 (Gal-9) reactivates latently HIV-infected cells in vitro and ex vivo , which may allow for immune-mediated clearance of these cells. However, Gal-9 also activates several immune cells, which could negatively affect HIV persistence by promoting chronic activation/exhaustion. This potential 'double-edged sword' effect of Gal-9 raises the question of the overall impact of Gal-9 on HIV persistence in vivo . We used the BLT (bone marrow, liver, thymus) humanized mouse model to evaluate the impact of Gal-9 on HIV persistence in vivo during antiretroviral therapy (ART). Two independent cohorts of ART-suppressed HIV-infected BLT mice were treated with either recombinant Gal-9 or phosphate-buffered saline control. Plasma viral loads and levels of tissue-associated HIV DNA and RNA were measured by qPCR. Immunohistochemistry and HIV RNAscope were used to quantify CD4 + T, myeloid, and HIV RNA+ cells in tissues. T cell activation and exhaustion were measured by flow cytometry, and plasma markers of inflammation were measured by multiplex cytokine arrays. Gal-9 did not induce plasma markers of inflammation or T cell markers of activation/exhaustion in vivo . However, the treatment significantly increased levels of tissue-associated HIV DNA and RNA compared to controls ( P  = 0.0007 and P  = 0.011, respectively, for cohort I and P  = 0.002 and P  = 0.005, respectively, for cohort II). RNAscope validated the Gal-9 mediated induction of HIV RNA in tissue-associated myeloid cells, but not T cells. Our study highlights the overall adverse effects of Gal-9 on HIV persistence and the potential need to block Gal-9 interactions during ART-suppressed HIV infection.