Human galectin-9 promotes the expansion of HIV reservoirs in vivo in humanized mice. Academic Article uri icon

Overview

abstract

  • OBJECTIVE: 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. DESIGN: 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). METHODS: Two independent cohorts of ART-suppressed HIV-infected BLT mice were treated with either recombinant Gal-9 or PBS 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. RESULTS: 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. CONCLUSIONS: 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.

publication date

  • November 28, 2022

Research

keywords

  • HIV Infections
  • HIV-1

Identity

Digital Object Identifier (DOI)

  • 10.1097/QAD.0000000000003443

PubMed ID

  • 36460646