Truncation of the human immunodeficiency virus-type-2 envelope glycoprotein allows efficient pseudotyping of murine leukemia virus retroviral vector particles

The incorporation of human immunodeficiency virus-type-2 (HIV-2) envelope g lycoprotein into murine leukemia virus (MuLV) particles was studied in a tr ansient transfection packaging cell system. We observed that wild-type HIV- 2 envelope protein or a frameshift mutant with 187 unrelated carboxyl-termi nal residues did not allow the formation of infectious retroviral particles . In view of recent findings that an HIV-1 envelope protein variant with a shortened cytoplasmic domain was incorporated into MuLV particles, we const ructed carboxyl-terminal truncations of the HIV-2 envelope protein. An enve lope variant with 18 cytoplasmic amino acids formed only very few viral pse udotypes. The further removal of an additional 11 amino acids allowed the e fficient pseudotyping of MuLV particles. As with the HIV-1 envelope protein , an HIV-2 envelope variant with 7 cytoplasmic amino acids was incorporated into functional MuLV particles. The pseudotyped vectors obtained are able to infect human CD4/CXCR4-expressing cells. Cell lines expressing human CD4 and other coreceptors could not be infected. This retroviral vector will p rove useful for the study of HIV infection events mediated by the HIV-2 env elope glycoproteins, as well as for the targeting of CD4+ cells in the cont ext of gene therapy of AIDS. (C) 1999 Academic Press.