Recent studies have established the involvement of HMGB1 in not only acute and chronic inflammatory conditions, including sepsis, 13 rheumatic diseases, 14 or SLE, 15 but also viral infectious diseases, such as that induced by SARS, hepatitis viruses, influenza viruses 16 or HIV. 17 It is currently unclear whether HMGB1-mediated inflammatory response contributes to the pathogenesis of various viral diseases, but it has been suggested to be involved in SARS-associated injurious pulmonary inflammatory response, persistent liver injury in hepatitis patients, or pathogenesis of West Nile encephalitis. 18 Regarding HIV infection, elevated plasma levels of HMGB1 were detected during progressive HIV-1 infection, positively associated with viral replication. 17 In vitro, HMGB1 may trigger or inhibit HIV-1 replication, depending on the target cell and the microenvironment. 19, 20 Recent studies analyzed the impact of HMGB1 on the fate of HIV-1-infected DCs, and the data suggested not only a possible contribution of this protein to the functional impairment of DCs but also to HIV dissemination and persistence. 21, 22 This review will discuss the mechanisms whereby HMGB1 contributes to innate immunity by regulating maturation and functions of DCs but also how it may contribute to viral latency and HIV disease pathogenesis.