Altered distribution of tissue galectins correlates with mucosal dysregulation in SIV infection.

Abstract

The intestinal mucosa in individuals with chronic human immunodeficiency virus (HIV) infection remains a site of viral persistence and immune dysregulation, even with prolonged suppressive antiretroviral therapy (ART). While biomarkers of mucosal damage and microbial translocation offer valuable correlative insights, the underlying mechanisms remain incompletely understood. Immunoregulatory galectins are implicated in HIV persistence and pathogenesis and play critical roles in intestinal inflammation and host-microbiome homeostasis. Here, we leveraged archival samples and data from an anti-α4β7 immunotherapy study of simian immunodeficiency virus (SIV)-infected rhesus macaques to investigate the relationships between circulating and gut mucosal galectins 1, 3, and 9, and barrier integrity, by tracking levels of tight junction proteins, and SIV viral load assessment of RNA and DNA levels in tissues. Elevated plasma levels of galectin-9 during peak viremia, ART suppression, ART interruption, and at necropsy were significantly correlated with SIVgag DNA levels in the ascending colon during necropsy. Several galectins were significantly reduced in the ascending colon and duodenum in ART-treated SIV-infected macaques compared to viremic animals and were related to tight junction disruptions. These findings suggest mucosal SIV burden and impaired gut integrity may be influenced by changes due to circulating and tissue galectins, making them potential therapeutic targets to restore gut homeostasis.