Potential roles of the innate immune system during HIV infection. (1) Following exposure at mucosal surfaces, HIV is transmitted with very low transmission efficiency, indicating that innate antiviral mechanisms are operative to prevent establishment of infection. (2) The early inflammatory response leads to recruitment and activation of various leukocytes, some of which serve as target cells for de novo HIV infection. (3) After acute infection, circulating viral load is generally decreased to a low level. This is mediated by the adaptive immune response, which is activated through processes driven by the innate immune response. Moreover, direct innate antiviral mechanisms contribute to control of virus replication during the chronic phase. (4) Persistent immune activation during chronic HIV infection involves activities stimulated by HIV-derived or opportunistic PAMPs through PRRs.