Truncation of the Human Immunodeficiency Virus-Type-2 Envelope Glycoprotein Allows Efficient Pseudotyping of Murine Leukemia Virus Retroviral Vector Particles

AbstractThe incorporation of human immunodeficiency virus-type-2 (HIV-2) envelope glycoprotein into murine leukemia virus (MuLV) particles was studied in a transient transfection packaging cell system. We observed that wild-type HIV-2 envelope protein or a frameshift mutant with 187 unrelated carboxyl-terminal 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 constructed carboxyl-terminal truncations of the HIV-2 envelope protein. An envelope variant with 18 cytoplasmic amino acids formed only very few viral pseudotypes. The further removal of an additional 11 amino acids allowed the efficient 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 prove useful for the study of HIV infection events mediated by the HIV-2 envelope glycoproteins, as well as for the targeting of CD4+ cells in the context of gene therapy of AIDS