title: Coreceptor Switch of [MLV(SIVagm)] pseudotype vectors by V3-loop exchange.
abstract: Retroviral vectors derived from murine leukemia virus (MLV) have been pseudotyped with a variant of the envelope glycoprotein (Env) of nonpathogenic simian immunodeficiency virus from African green monkeys (SIVagm) to result in [MLV(SIVagm-wt)] vector particles. The variant env gene encodes a full-length surface envelope glycoprotein (SU) and a C-terminally truncated transmembrane protein (TM). To change the coreceptor usage of this vector from CCR5 to CXCR4, which is predominant on human CD4-positive lymphocytes, the putative V3-loop of SIVagm SU was replaced by that of the T cell tropic HIV-1 variant BH10. The resulting [MLV(SIVagm-X4)] vectors were shown to specifically transduce CD4/CXCR4-positive cell lines, demonstrating the equivalent function in cell entry and choice of coreceptor usage of the V3-loops of SIVagm and HIV-1. These modified vectors were able to transduce primary human lymphocytes and were resistant to neutralization by sera from HIV-1-infected individuals. The [MLV(SIVagm-X4)] pseudotype vector generated is thus a promising candidate vector, e.g., for in vivo gene therapy of HIV-1 infection.
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000628:therapy; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D015686:Gene Products, env / Q000737:chemistry* / Q000502:physiology; D015316:Genetic Therapy; D005822:Genetic Vectors; D015497:HIV-1 / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics*; D008969:Molecular Sequence Data; D019713:Receptors, CCR5 / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000502:physiology*; D015302:Simian Immunodeficiency Virus / Q000737:chemistry* / Q000502:physiology; D019065:Virus Assembly
chemical_list: D015686:Gene Products, env; D019713:Receptors, CCR5; D019718:Receptors, CXCR4