HSV-1 immune escapes in microglia by down-regulating GM130 to inhibit TLR3-mediated innate immune responses

Purpose To investigate the mechanism of GM130 regulating the antiviral immune response of TLR3 after HSV-1 infection of microglia cells. To explore the regulatory of berberine on GM130 and TLR3 mediated immune response. Methods The vitro model of HSV-1 infection was established by infecting BV2 cells with HSV-1. Results Compared with the uninfected group, the Golgi apparatus fragmentation and GM130 decrease after HSV-1 infected; TLR3 increased at 6h and began to decrease at 12h after HSV-1 infected ; the secretion of IFN-β, TNF-α and IL-6 increased after infection. Knockdown of GM130 aggravated the fragmentation of Golgi apparatus, and caused TLR3 to further decrease, and the virus titer also increased significantly. Knockdown of GM130 can inhibit the increase of TLR3 and inflammatory factors induced by TLR3 agonists and increase the viral titer. Over-expression of GM130 alleviated the Golgi fragmentation induced by HSV-1, partially restored the level of TLR3, and reduced the viral titer. Over-expression of GM130 reversed the reduction of TLR3 and inflammatory cytokines induced by TLR3 inhibitors. Therefore, the decrease in GM130 caused by HSV-1 infection will lead to increased viral replication by inhibiting TLR3-mediated innate immunity. Berberine can protect the Golgi apparatus and reverse the down-regulation of GM130, as well as reverse the down-regulation of TLR3 and its downstream factor factors after HSV-1 infection, reducing the virus titer. Conclusion In microglia, HSV-1 immune escapes by causing the GM130/TLR3 pathway to affect the secretion of inflammatory cytokines. Berberine protects the Golgi apparatus and enhances TLR3 mediated antiviral immune response.