Cellular factors associated with entry of HIV-1 strain 89.6

Kelly Anne Stefano, University of Pennsylvania


Many important questions about the pathogenesis of human immunodeficiency virus type 1 (HIV-1) exist. Basic questions about the differences in the ability of different HIV-1 strains to infect and replicate in various cell types, and the cellular responses involved in this HIV-1 infection are key to our understanding of the pathogenesis of disease. In addressing differences in cellular tropism, it is important to first address the complex mechanism of viral entry. While the initial events involved in HIV-1 infection are still largely undefined, understanding these early events in viral entry is crucial if we are to understand the manifestation of disease. We have focused primarily on those secondary mechanisms involved in entry of a unique strain of HIV-1 into cell lines in vitro. To address this question, we utilized a T cell/B cell hybrid line, CEMx174, as well as a series of recombinant viruses constructed from a recently cloned M-tropic isolate, HIV-1(89.6), and a prototype L-tropic strain, HIV-1(IIIB), to analyze the cellular and viral determinants involved in entry of HIV-1(89.6). The studies described provide evidence for (i) the involvement of HIV-1 env region(s), outside of the V3 loop and the CD4-binding domain, which may also act in a virus strain-specific manner to determine cellular tropism; and (ii) the existence of a cellular factor that acts at a post-binding step to modulate CD4-mediated entry in a virus strain-specific and possibly also a cell type-specific manner. Our observations demonstrate the need for additional cellular factors for the CD4-mediated entry of HIV-1(89.6) in our cell system. In addition, we identify two potential cell-specific factors, the protein tyrosine kinase p56lck and a B cell-specific surface marker, that may be involved in the virus strain-specific entry into CEMx174 cells. While these cellular and viral determinants may vary for individual strains of HIV-1, identification of the mechanism that facilitates CD4-dependent entry in this system may lend insight into the entry process in primary cells.

Subject Area

Microbiology|Immunology|Cellular biology

Recommended Citation

Stefano, Kelly Anne, "Cellular factors associated with entry of HIV-1 strain 89.6" (1994). Dissertations available from ProQuest. AAI9427620.