Acquired immune deficiency Syndrome (AIDS) is a slow degenerative disease of the immune and nervous systems resulting from a chronic and persistent infection by the human immunodeficiency virus type-1 (HIV-1), a retrovirus that belongs to the lentivirus subfamily. Despite considerable progress made in our comprehension of HIV-1 infection, we still do not completely understand how the virus causes disease and how it persists in infected individuals in presence of a vigorous immune response and highly suppressive antiretroviral regimens. One of the defining features of primate immunodeficiency viruses is that they encode a number of accessory proteins, Vif, Vpr/Vpx, Vpu and Nef, which are not commonly found in other retroviruses; overall, the function of these viral proteins is to interact with fundamental host cell processes to modify the local environment within infected cells to ensure efficient replication and transmission as well as immune evasion. The overall goal of the research projects pursued in the Human Retrovirology unit is to understand the functional role of the Vpr (Viral protein R) and Vpu (Viral protein U) accessory proteins during viral during HIV-1 infection and pathogenesis and to elucidate in molecular and cellular terms their mechanism of action. Through the study of these accessory proteins, researchers and graduate students of the unit are investigating post-entry restrictions during HIV infection of macrophages, interactions between HIV-1 and effectors of the host innate immune response, HIV interactions with the host ubiquitin machinery as well as the molecular and cellular processes governing HIV-1 assembly, release and transmission. Ultimately, the elucidation of the interaction between HIV-1 accessory proteins and host cells will lead to an improved understanding of viral replication and pathogenesis as well as suggesting additional targets for antiviral and vaccine interventions.