Strengthening and Sustaining Inter-Institutional Research Collaborations and Partnerships.

Inter-institutional collaborations and partnerships play fundamental roles in developing and diversifying the basic biomedical, behavioral, and clinical research enterprise at resource-limited, minority-serving institutions. In conjunction with the Research Centers in Minority Institutions (RCMI) Program National Conference in Bethesda, Maryland, in December 2019, a special workshop was convened to summarize current practices and to explore future strategies to strengthen and sustain inter-institutional collaborations and partnerships with research-intensive majority-serving institutions. Representative examples of current inter-institutional collaborations at RCMI grantee institutions are presented. Practical approaches used to leverage institutional resources through collaborations and partnerships within regional and national network programs are summarized. Challenges and opportunities related to such collaborations are provided.

HIV-1 Nef protein is secreted into vesicles that can fuse with target cells and virions.

HIV-1 Nef is a major determinant in HIV-1 pathogenicity. However, its properties have mainly been associated with its biochemical activities within the producer cell. Nef is also secreted from infected and transfected cells. Our primary objective was to determine the nature of secreted Nef protein and its effect on target cells. We determined that HIV-1 Nef is secreted in the form of exosome-like vesicles. Nef protein present in these vesicles is largely protected from protease digestion, which suggests that most of the protein is present on the lumenal side of the vesicles. We observed that HEK293 cells, transfected with a Nef-GFP expression vector, can secrete vesicles containing Nef-GFP fusion protein into the extracellular medium. When the conditioned medium was used to treat Jurkat cells, we found that the cells can take up the Nef fusion protein. The pattern of distribution of the Nef-GFP fusion protein within the target cells is mainly cytoplasmic and results in a punctate staining pattern. We also observed that Nef (-) virions treated with Nef-conditioned medium have their infectivity restored to near wild-type levels. This implies that the Nef contained within vesicles has the ability to fuse with HIV-1 virions and deliver functional Nef to these virions. It also demonstrates that Nef protein delivered in trans can restore infectivity even after virion maturation has occurred. These studies suggest that secreted Nef could play a role in HIV-1 pathogenesis by inducing effects in noninfected bystander cells.