AN INFECTIOUS CHIMERIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 (HIV-2) EXPRESSING THE HIV-1 PRINCIPAL NEUTRALIZING DETERMINANT

The human immunodeficiency virus type 1 strain MN (HIV-1(MN)) principa l neutralizing determinant (PND, V3 loop) was introduced into infectio us molecular clones HIV-2(KR) and simian immunodeficiency virus mm239 (SIVmm239) by hybridization PCR, replacing the corresponding HIV-2 or SIV envelope cysteine loops with the HIV-1 coding sequence. The HIV-2 chimera (HIV-2(KR-MNV3)) was found to be capable of infecting a number of T-cell lymphoblastic cell lines as well as primary peripheral bloo d mononuclear cells. In contrast, the SIV chimera (SIV239MNV3) was not replication competent. Envelope produced by HIV-2(KR-MNV3) but not th e parental HIV-2(KR) was recognized by V3-specific and HIV-1-specific polyclonal antisera in radioimmunoprecipitation assays. HIV-2-specific antisera recognized both the chimeric and parental virus but not HIV- 1(MN). The chimeric HIV-2(KR-MNV3) virus proved to be exquisitely susc eptible to neutralization by HIV-1-specific and V3-specific antisera, suggesting the potential for use in animal models designed to test HIV -1 vaccine candidates which target the PND.