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Journal of Virology, January 2002, p. 19-31, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.19-31.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Rhabdovirus-Based Vectors with Human Immunodeficiency Virus Type 1 (HIV-1) Envelopes Display HIV-1-Like Tropism and Target Human Dendritic Cells

Heather D. Foley,1,2 Miguel Otero,1,3 Jan M. Orenstein,4 Roger J. Pomerantz,1,3,5 and Matthias J. Schnell1,5*

The Dorrance H. Hamilton Laboratories, Center for Human Virology,1 Microbiology and Immunology,2 Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107,3 Department of Pathology, George Washington University Medical Center, Washington, D.C. 20037,4 Departments of Biochemistry and Molecular Pharmacology5

Received 7 August 2001/ Accepted 5 October 2001

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-189.6 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.

* Corresponding author. Mailing address: 1020 Locust St.,Suite 335, Philadelphia, PA 19107-6799. Phone: (215) 503-1260. Fax: (215) 923-1956. E-mail: matthias.schnell{at}mail.tju.edu.

Journal of Virology, January 2002, p. 19-31, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.19-31.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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