CD4 and HIV infectious disease: These include (i) a privileged tissue architecture that favors close cellular contact between immune cells, thereby promoting cell-to-cell transmission of HIV and ensuring viral dissemination; (ii) a significant enrichment in the frequency of cells that are highly permissive to HIV infection, such as activated CD4+ T cells that can produce large numbers of viral particles; and (iii) a proinflammatory environment that enhances viral production from infected cells and promotes new infections.