Rhabdovirus-based vectors with human immunodeficiency virus type 1 (HIV-1) envelopes display HIV-1-like tropism and target human dendritic cells

被引:29
作者
Foley, HD
Otero, M
Orenstein, JM
Pomerantz, RJ
Schnell, MJ
机构
[1] Thomas Jefferson Univ, Jefferson Med Coll, Dorrance H Hamilton Labs, Ctr Human Virol, Philadelphia, PA 19107 USA
[2] Thomas Jefferson Univ, Jefferson Med Coll, Dept Mol Pharmacol & Biochem, Philadelphia, PA 19107 USA
[3] Thomas Jefferson Univ, Jefferson Med Coll, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA
[4] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA
[5] George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA
关键词
D O I
10.1128/JVI.76.1.19-31.2002
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 I (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.
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页码:19 / 31
页数:13
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