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Microbes Infect. 2017 Apr - May;19(4-5):277-287. doi: 10.1016/j.micinf.2016.12.004. Epub 2016 Dec 24.

A recombinant vesicular stomatitis virus encoding CCR5-tropic HIV-1 receptors targets HIV-1-infected cells and controls HIV-1 infection.

Author information

1
Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo, Japan. Electronic address: kokuma@niid.go.jp.
2
Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo, Japan; Technology and Product Development Division, Diagnostic Reagent Development, Sysmex Corporation, Kobe, Japan.
3
Technology and Product Development Division, Diagnostic Reagent Development, Sysmex Corporation, Kobe, Japan.
4
Central Institute of Experimental Animals, Kanagawa, Japan.
5
Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
6
Department of Pathology, Yale University School of Medicine, CT, USA.
7
Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo, Japan.

Abstract

Anti-retroviral therapy is useful to treat human immunodeficiency virus type 1 (HIV-1)-infected individuals, but has some major problems, such as the generation of multidrug-resistant viruses. To develop a novel supplemental or alternative therapeutic for CCR5-tropic (R5) HIV-1 infection, we generated a recombinant vesicular stomatitis virus (rVSV) in which the gene encoding its envelope glycoprotein (G) was replaced with the genes encoding R5 HIV-1 receptors (human CD4 and CCR5), designated VSVΔG-CC5. Our present data demonstrate that this rVSV specifically infects cells that are transiently expressing R5 HIV-1 envelope glycoproteins, but does not infect those expressing CXCR4-tropic HIV-1 envelope glycoproteins. Notably, after a CD4+CCR5+ T cell line or primary cells initially infected with R5 HIV-1 were inoculated with G-complemented VSVΔG-CC5, the rVSV significantly reduced the number of HIV-1-infected cells, probably through direct targeting of the rVSV and VSV-mediated cytolysis and/or through syncytium formation- or cell-cell fusion-dependent killing, and markedly inhibited HIV-1 production. Furthermore, G-complemented VSVΔG-CC5 also efficiently inhibited HIV-1 infection in R5 HIV-1-infected humanized immunodeficient mice. Taken together, our findings indicate that a cytolytic rVSV that targets and eliminates R5 HIV-1-infected cells potentially has therapeutic value for controlling R5 HIV-1 infection.

KEYWORDS:

Envelope; Human immunodeficiency virus type 1; Infection; Receptor; Therapy; Vesicular stomatitis virus

PMID:
28025070
DOI:
10.1016/j.micinf.2016.12.004
[Indexed for MEDLINE]

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