Rhabdovirus-based vectors with human immunodeficiency virus type 1 (HIV-1) envelopes display HIV-1-like tropism and target human dendritic cells.
Enviado por Miguel Otero el
Título | Rhabdovirus-based vectors with human immunodeficiency virus type 1 (HIV-1) envelopes display HIV-1-like tropism and target human dendritic cells. |
Publication Type | Journal Article |
Year of Publication | 2002 |
Autores | Foley, HD, Otero, M, Orenstein, JM, Pomerantz, RJ, Schnell, MJ |
Journal | J Virol |
Volume | 76 |
Issue | 1 |
Pagination | 19-31 |
Date Published | 2002 Jan |
ISSN | 0022-538X |
Palabras clave | AIDS Vaccines, Antibodies, Monoclonal, Antigens, CD4, Cells, Cultured, Chemokines, Dendritic Cells, Gene Targeting, Genetic Vectors, HIV Envelope Protein gp160, HIV-1, Humans, Rabies virus, Receptors, CXCR4, Virulence, Virus Replication |
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. |
Alternate Journal | J. Virol. |
PubMed ID | 11739668 |
PubMed Central ID | PMC135731 |
Grant List | AI44340 / AI / NIAID NIH HHS / United States AI49153 / AI / NIAID NIH HHS / United States |