CD4(-) epithelial cells covering mucosal surfaces serve as the primary barr
ier to prevent human immunodeficiency virus type I (HIV-1) infection. We us
ed HIV-1 vectors carrying the enhanced green fluorescent protein gene as a
reporter gene to demonstrate that HIV-1 can infect some CD4- human epitheli
al cell lines with low but significant efficiencies. Importantly, HIV-1 inf
ection of these cell lines is independent of HIV-1 envelope proteins. The E
nv-independent infection of CD4- cells by HIV-1 suggests an alternative pat
hway for HIV-1 transmission. Even on virions bearing Env, a neutralizing an
tibody directed against gp120 is incapable of neutralizing the infection of
these cells, thus raising potential implications for HIV-1 vaccine develop
ment.