HIV type 1 infection of human astrocytes is restricted by inefficient viral entry

The mechanism by which HIV infects astrocytes is not known. We used the sim ian virus 40 (SV40)-transformed human astrocyte cell line, SVG-A, to invest igate HIV infection of astrocytes. We previously reported that SVG-A cells are susceptible to low levels of CD4/CXCR4-independent infection by an X4 s train of HIV-1. Infection was greatly increased when the prototypical X4 re ceptors, CD4 and CXCR4, were expressed on the SVG-A cells (SVGCD4-X4). Thes e data suggest that HIV-1 enters astrocytes by a novel mechanism that is in efficient compared with CD4/CXCR4-mediated entry. In this article, we repor t high levels of early viral gene expression in both SVG-A and SVGCD4-X4 ce lls once the HIV entry pathway is circumvented. These data indicate that HI V-1 infection of SVG-A cells is restricted by inefficient viral entry rathe r than by post-entry events. As we were unable to detect infection of nontr ansformed primary astrocytes, we investigated whether SV40 transformation a ffects the susceptibility of astrocytes to HIV infection. To study this, we transformed primary fetal and adult astrocytes with the same origin-defect ive SV40 mutant that was used to transform the SVG-A cell line. We found th at SV40 transformation did not alter the susceptibility of astrocytes to HI V infection. Furthermore, high levels of early viral gene expression were d etected in these cells once the HIV entry process was by-passed. Taken toge ther, the results of these studies indicate that HIV infection of human ast rocytes is restricted by inefficient viral entry.