SIVmac Expressing Hybrid Envelope Proteins Containing HIV-1 V3 and/or C4 Sequences is Not Competent for Replication

The V3- and C4-coding regions in the envelope gene of the infectious, pathogenic SIVmac239 clone were replaced by the corresponding HIV-l sequences. Viral particles were obtained after transfection of COS-1 cells. Chimeric SIVmac constructs were not replication competent in the human T cell lines CEMx174, AA2, H9, and MT-4 or in primary cultures of rhesus monkey peripheral blood mononuclear cells. The lack of infectivity of the hybrid constructs was associated with inefficient proteolytic processing of the gp160^env precursor. Unlike the modular nature of some proteins, gp 120 appears to be a highly ordered molecule whose function is dependent on the integration of many discontinuous, interactive regions.