7th International AIDS Conference Florence, Italy — June 16-21, 1991

Int Conf AIDS 1991 Jun 16-21; 7:98 (abstract no. M.A.1026)
Levy DN, Williams WV, Weiner DB; University of Pennsylvania, Philadelphia, Pennsylvania, USA

OBJECTIVE: The cellular tropism of HIV is determined by the envelope proteins. The precursor glycoprotein gp160 is post-translationally cleaved to yield gp120 and gp41. The external glycoprotein gp120 is noncovalently attached to gp41 and mediates virus binding to the T cell antigen CD4. The transmembrane glycoprotein gp41 mediates virus fusion with the cell membrane following virus attachment. Cells that are infected with HIV express gp120 and gp41 on their surface. Retroviral mediated transfer of genes and/or pharmacologically active agents is a promising method for treatment for various diseases including viral infection. An important ingredient in such a system is the ability to specifically target a retroviral vector to the cells of interest.

METHODS: In order to study determinants of viral tropism and to develop a system for specifically targeting retroviral vectors to HIV infected cells we have constructed chimeric HIV envelope proteins in which the determinants of virus binding have been replaced with determinants of other proteins involved in receptor-ligand interactions. Among these we have created chimeric proteins in which the CD4 binding domain of gp120 is replaced by the gp120 binding domain of CD4.

RESULTS: We have expressed these proteins in mammalian cells and examined their expression and function with respect to protein folding, cleavage of gp160 into gp120 and gp41, transport to the cell surface, binding to native gp120, fusion with HIV envelope expressing cells, and incorporation into viral particles.

DISCUSSION: These studies suggest that chimeric proteins can have utility in retroviral targeting.

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