gp120-Independent infection of CD4(-) epithelial cells and CD4(+) T-cells by HIV-1

Infection of CD4- cells by HIV-1 is well documented, but the mechanism responsible remains a matter of discussion. Previously we modified an HIV-1 virus strain, NL4-3, by deleting the Env proteins (gp41 and gp120) and inserting the enhanced green fluorescent protein (EGFP), and found that the Env(-) virus infects several types of CD4- cells. Here, we have prepared Env(-) virus from both the CD4- cell line, 293T, and the CD4+ cell lines, CEM and SUPT1, and found that HIV-1 Env(-) virus from either cell type is infectious for both CD4+ and several CD4- cell lines. Replication of HIV-1 Env(-) virus-infected cells was demonstrated by p24 gag protein assays and real-time reverse transcriptase polymerase chain reaction (RT-PCR) of the culture medium from infected cells. Virus collected from the HIV-1-Env(-) infected cultures proved infectious to several CD4- cell lines. Our results suggest that HIV-1 infects both CD4- and CD4+ cells using a gp120-independent mechanism. This infection mechanism may provide new explanations for HIV-1 latency and persistent infection in patients.