title: Rhabdovirus-based vectors with human immunodeficiency virus type 1 (HIV-1) envelopes display HIV-1-like tropism and target human dendritic cells.
abstract: We describe replication-competent, vaccine strain-based rabies viruses (RVs) that lack their own single glycoprotein and express, instead, a chimeric RV-human immunodeficiency virus type 1 (HIV-1) envelope protein composed of the ectodomain and transmembrane domains of HIV-1 gp160 and the cytoplasmic domain of RV G. The envelope proteins from both X4 (NL4-3)- and R5X4 (89.6)-tropic HIV-1 strains were utilized. These recombinant viruses very closely mimicked an HIV-1- like tropism, as indicated by blocking experiments. Infection was inhibited by SDF-1 on cells expressing CD4 and CXCR4 for both viruses, whereas RANTES abolished infection of cells expressing CCR5 in addition to CD4 in studies of the RV expressing HIV-1(89.6) Env. In addition, preincubation with soluble CD4 or monoclonal antibodies directed against HIV-1 gp160 blocked the infectivity of both G-deficient viruses but did not affect the G-containing RVs. Our results also indicated that the G-deficient viruses expressing HIV-1 envelope protein, in contrast to wild-type RV but similar to HIV-1, enter cells by a pH-independent pathway. As observed for HIV-1, the surrogate viruses were able to target human peripheral blood mononuclear cells, macrophages, and immature and mature human dendritic cells (DC). Moreover, G-containing RV-based vectors also infected mature human DC, indicating that infection of these cells is also supported by RV G. The ability of RV-based vectors to infect professional antigen-presenting cells efficiently further emphasizes the potential use of recombinant RVs as vaccines.
authors.affiliation: The Dorrance H. Hamilton Laboratories, Center for Human Virology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Heather D
authors.initials: HD
authors.lastname: Foley
authors.forename: Miguel
authors.initials: M
authors.lastname: Otero
authors.forename: Jan M
authors.initials: JM
authors.lastname: Orenstein
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Pomerantz
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Schnell
mesh_terms: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D018390:Gene Targeting; D005822:Genetic Vectors; D019302:HIV Envelope Protein gp160 / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D011820:Rabies virus / Q000235:genetics* / Q000472:pathogenicity; D019718:Receptors, CXCR4 / Q000378:metabolism; D014774:Virulence / Q000276:immunology; D014779:Virus Replication
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D018925:Chemokines; D019302:HIV Envelope Protein gp160; D019718:Receptors, CXCR4