What are the molecular mechanisms involved in vivo in the disruption of NK cell-DC cross talk during chronic HIV-1 infection, and what are the consequences on both NK cell killing activity and DC-dependent promotion of adaptive immune responses? Does HMGB1 has a role in the trans-infection of T lymphocytes with HIV-1 through the exosome-dissemination pathway? Given that HMGB1 can combine with LPS to trigger TLRs, and TLR-mediated immune activation results in the production of proinflammatory cytokines, to what extent does HMGB1 contribute to generalized immune activation and disease progression in HIV-1-infected individuals? What is the contribution of HMGB1 to HIV dissemination and the establishment of HIV reservoirs in DCs? Would the specific targeting of c-FLIP or c-IAPs in DCs contribute to the depletion of HIV-1 reservoirs? Given the expression of HMGB1 and its receptor RAGE in active neurological diseases, including multiple sclerosis and Alzheimer's disease, does it has a role in HIV-associated neurological disorder?