The dual roles of EVs during HIV-1 infection. The EVs released upon HIV-1 infection have shown to have antiviral and proviral functions. EVs contribute to suppress HIV infection by limiting viral replication or enhancing antiviral immunity. CD4-containing EV may serve as a decoy for CD4 T cells and neutralize HIV-1 virions. Exosomal cargo such as APOBEC3G (A3G) inhibit HIV-1 replication. EVs can transport ISGs such as ISG15, ISG56, and MX2 trigger antiviral immunity and EVs derived from bodily fluids such as breast milk, semen, and vaginal fluids can hider HIV-1 infection. However, EVs also can promote HIV-1 infection and pathogenesis. Co-receptors such as CCR5 or CXCR4 can be delivered to neighboring cells via EVs, enhancing susceptibility to HIV-1 infection. TIM-4-containing EVs assit trafficking of HIV-1 to immune cells. EVs can carry TAR element RNA to enhance susceptibility to HIV-1 infection in undifferentiated immune cells. Transport viral component by EVs may enhance viral entry and infectivity. EV-mediated transport of HIV-1 Nef protein may lead viral-mediated apoptosis of immune cells. Well-known TNFα converting enzyme ADAM17 can be loaded into EVs. These EVs can contribute to chronic inflammation by secretion of mature TNFα. Host-derived miRNAs or viral miRNAs can be transported by EVs, resulting in enhancement of HIV-1 infection and chronic immune activation, leading to HIV-1 pathogenesis.
