Gene expression profiling of gut mucosa and mesenteric lymph nodes in simian immunodeficiency virus-infected macaques with divergent disease course

Background: Although the majority of drug-naïve HIV-infected patients develop acquired immunodeficiency syndrome (AIDS), a small percentage remains asymptomatic without therapeutic intervention. Methods: We have utilized the simian immunodeficiency virus (SIV)-infected rhesus macaque model to gain insights into the molecular mechanisms of long-term protection against simian AIDS. Results: Chronically SIV-infected macaques with disease progression had high viral loads and CD4⁺ T-cell depletion in mucosal tissue and peripheral blood. These animals displayed pathologic changes in gut-associated lymphoid tissue (GALT) and mesenteric lymph node that coincided with increased expression of genes associated with interferon induction, inflammation and immune activation. In contrast, the animal with long-term asymptomatic infection suppressed viral replication and maintained CD4⁺ T cells in both GALT and peripheral blood while decreasing expression of genes involved in inflammation and immune activation. Conclusions: Our findings suggest that reduced immune activation and effective repair and regeneration of mucosal tissues correlate with long-term survival in SIV-infected macaques.