Gp120 can contribute to enhanced HIV-1 infection of the CNS and the corresponding neuroinflammation through disruption of the BBB, increased cytokine secretion, specifically TNFα via activation of microglia and astrocytes, and increased neuronal sensitivity to calcium fluctuation [36,37,38,39,40,41,42,43]. This evidence concerns the gene ITIH4 and HIV-1 infection.