Grant: Travel Awards - Institute Community Support

HIV-1 dissemination from the genital mucosal tract to the lymphoid organs is the first critical step towards systemic infection. HIV-1 can disseminate either as free-virus that passively enters the blood and lymphatics, or it can be actively transported to lymphoid tissues by migratory cells. At the genital mucosal tract, dendritic cells (DCs) are proposed to be among the first cells that encounter HIV at the mucosal surface during sexual transmission. They are the only migratory cells consistently operating at the interface of innate and adaptive immunity. Hence, HIV-1 virus hijacks DC's capability and use it as a cellular ferry to reach its major target, CD4 T cells in the lymphoid tissue and cause explosive viral replication and dissemination. This mechanism will lead to the progressive depletion of CD4 T cells and establish viral reservoirs that cannot be eliminated. However, the underlying molecular and cellular mechanism requirements of migratory DCs that spread HIV from the initial site of viral entry to the lymphoid tissues remain unknown. Therefore, we will address the role of migratory DCs in HIV dissemination using the experimental conditions that more closely recapitulates their natural behaviors. We anticipate that this study will uncover a novel approach to restrain virus dissemination from the entry site in genital mucosa and prevent systemic infection during acute HIV infection.