VPX mutants of HIV-2 are infectious in established cell lines but display a severe defect in peripheral blood lymphocytes.

Nucleotide sequence comparison between HIV-1, HIV-2 and SIV has revealed the presence of an open reading frame (ORF) in the central region of the genomes of HIV-2 and SIV that has no counterpart in HIV-1. This new ORF, called vpx, is highly conserved between HIV-2ROD and SIVmac. Using anti-peptide sera to the predicted protein and site-directed mutagenesis, we show that mutations in the vpx ORF eliminate the synthesis of a 16 kd protein in HIV-2 infected cells, confirming that this protein is the product of this gene. Full-length clones of HIV-2 containing these mutations are infectious in two permanent T lymphocytic cell lines and two monocytic cell lines. In contrast, we show that loss of VPX function results in a severe defect in the productive infection of human peripheral blood lymphocytes both in the amount of reverse transcriptase activity produced and in core protein expression. These findings suggest that the VPX protein plays an important role in the in vivo life cycle of the HIV-2/SIV viruses.