Entry of human immunodeficiency virus-1 into glial cells proceeds via an alternate, efficient pathway

Although the CD4 molecule is the cellular receptor for human immunodeficiency virus-1 (HIV-1) in cells of the lymphocyte/monocyte lineage, a number of investigators have also been able to infect cells, including several of central nervous system (CNS) origin, that do not express CD4 protein or mRNA. These infections are generally nonpermissive. To ascertain whether the nonpermissive nature of infection in glial cells is due to an inefficient entry pathway, we prepared a permanently transfected U373-MG cell line expressing the CD4 molecule and demonstrated that HIV-1 still replicates at a low level. Furthermore, a virus uptake assay indicated that HIV-1 enters glial cells effectively, even in the absence of CD4. These results demonstrate that HIV-1 entry is efficient and that the restrictive nature of the infection in glial cells is due to postentry mechanisms. In addition, these findings support the existence of an alternate, efficient, entry pathway in some glial cells.