HeLa cell lines producing infectious replication-defective HIV virions with varyinggp160 densities indicate that increasing cellulargp160 levels cause an increase in cell-to-cell fusion, while increasing viralgp160 levels exert a biphasic effect on infectivity

Abstract

Although the density of the HIV envelope protein (gp160) can vary on cells and virions, there has been little investigation into how the levels affect HIV infection and cell-to-cell fusion. To address this several cell lines stably producing infectious, replication defective virions of the T-cell line adapted HIV isolate, HXB2, were made. The cell lines varied from one another in gp160 surface expression over a five-fold range, while expressing similar levels of the Gag polyprotein. As a consequence, the cell lines collectively produced virus that varied in gp160 content over a six-fold range. With the cell lines it was observed that increasing gp160 surface expression increases cell-to-cell fusion efficiency and syncytium size. With the virus preparations it was found that gp160 levels had a biphasic affect on infection efficiency. Virus preparations with gp160 levels of 10-30 molecules per virion showed that increased gp160 content correlated with increased infection efficiency. However, at gp160 levels above 50 molecules per virion there was a decrease in infection efficiency associated with increasing gp160 per virion content. Therefore, it appears that increasing gp160 surface density exerts a qualitatively different affect on infection and cell-to-cell fusion. Based upon functional analysis, several cell lines producing the gp160 molecule from the primary isolate, JR-FL were also made. These cell lines were less characterized, and yet have the potential to be useful reagents in HIV research as well.