LncRNA SNHG1 Knockdown Ameliorates HIV-1 gp120V3 Loop-Induced Microglial Neuroinflammation by Regulating the Autophagy Process

HIV-1-associated neurocognitive disorders (HAND) are characterized by chronic CNS inflammation. Previous studies have shown that HIV-1 gp120 causes learning and memory deficits in mice and neuroinflammation in neurons and microglia through impaired autophagy. However, the regulation of autophagy in this context is unclear. We found that lncRNA SNHG1 is upregulated in HIV-1 gp120-induced microglial inflammation. Reducing SNHG1 levels alleviates this inflammation by increasing early autophagy protein ULK1, decreasing late autophagy protein p62, and enhancing the LC3B II/I ratio. Autophagy inhibitors 3-MA and CQ can reverse or enhance the effects of SNHG1 knockdown on microglial inflammation. The study suggests that knocking down lncRNA SNHG1 may enhance early autophagy initiation and late degradation, reducing neuroinflammation. The Wnt pathway inhibitor FH535 further improved this effect by increasing ULK1 protein and the LC3B II/I ratio. In contrast, the Sirt1 inhibitor EX527 activated the Wnt pathway, decreased the LC3B II/I ratio, and worsened neuroinflammation. Thus, lncRNA SNHG1 knockdown might regulate autophagy via the Sirt1-Wnt pathway to alleviate HIV-1 gp120-induced neuroinflammation, offering a new approach for HAND prevention and treatment.