Evaluating the role of Vimentin in Establishment of HIV-1 Infection in Macrophages

Evaluating the role of Vimentin in Establishment of HIV-1 Infection in Macrophages

The study conducted is aimed at determining the interaction between the cytoskeleton of macrophages and the human immunodeficiency virus (HIV-I). Monocytes/macrophages have been identified as one of the major HIV-I reservoirs harboring and disseminating the virus during the course of infection. Vimentin is an intermediate filament abundantly expressed in most human cell, including monocytes. Simialr to other intermediate filaments, vimentin is important for maintained of cell architecture. However, animals with knocked down vimentin have had remarkably normal phenotype. Since vimentin is cleaved by HIV-I encoded proteases, it has been suggested that vimentin may play a role in HIV infection. Preliminary data has shown that treatment with anti-vimentin antibody inhibits production of the virus by macrophages. To further develop and strengthen these observations we will investigate the steps of viral life cycle at which association of HIV-I with vimentin is required for the establishment of infection in macrophages. Using primary macrophage cultures, immunoprecipitation, and Western blotting we will attempt to identify the viral protein that interacts with vimentin. The study is expected to establish the role of vimentin in HIV-I infection of macrophages and provide data that can be exploited for a new treatment strategy targeting HIV-I reservoirs in macrophages.