Thus, contrary to the prevailing view that early HIV infection triggers brain inflammation primarily through microglia and astrocyte activation (Jia and Brew, 2025, Kong et al., 2024), our findings suggest that Tat-induced IL-6/JAK/STAT3 signaling in ECs may represent an alternative early mechanism by which HIV-1 entry across the BBB promotes endothelial injury and inflammation. The gene discussed is IL6; the disease is HIV infectious disease.