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A recombinant vesicular stomatitis virus encoding HIV-1 receptors and human OX40 ligand efficiently eliminates HIV-1-infected CD4-positive T cells expressing OX40.

Abstract
OX40 protein is highly expressed on activated CD4-positive T cells that are susceptible for human immunodeficiency virus type 1 (HIV-1) infection. To target and kill HIV-1-infected OX40(+) T cells, we used a recombinant vesicular stomatitis virus (rVSV) lacking its envelope glycoprotein (ΔG) and instead expressing HIV-1 receptors CD4/CXCR4 and OX40 ligand (OX40L). Expression of OX40L as well as HIV-1 receptors on the VSV particles led to specific infection of OX40(+) T cells, including primary cells, either acutely or chronically infected with X4 HIV-1. Consequently, the rVSV rapidly eliminated these infected cells and caused a marked reduction of HIV-1 viral load in culture. Inclusion of the OX40L gene in the VSV recombinant led to significantly better infection and HIV-1 elimination compared with an rVSVΔG expressing only HIV-1 receptors. A novel rVSVΔG encoding both HIV-1 receptors and OX40L has a potentially greater therapeutic value than an rVSVΔG expressing only HIV-1 receptors.
AuthorsChikayuki Tsuruno, Kazu Okuma, Yoshiaki Takahashi, Reiko Tanaka, Yuetsu Tanaka, Youichi Takahama, Yukio Hamaguchi, Isao Hamaguchi, Kazunari Yamaguchi
JournalHuman immunology (Hum Immunol) Vol. 72 Issue 4 Pg. 295-304 (Apr 2011) ISSN: 1879-1166 [Electronic] United States
PMID21262309 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
Chemical References
  • CD4 Antigens
  • OX40 Ligand
  • Receptors, CXCR4
  • Receptors, OX40
Topics
  • Animals
  • CD4 Antigens (genetics, immunology, metabolism)
  • CD4-Positive T-Lymphocytes (immunology, virology)
  • Cell Line
  • Cell Line, Tumor
  • Cricetinae
  • Gene Order
  • Genetic Vectors (genetics, isolation & purification, metabolism)
  • Giant Cells (metabolism, pathology)
  • HEK293 Cells
  • HIV Infections (immunology, virology)
  • HIV-1 (immunology, metabolism)
  • Humans
  • OX40 Ligand (genetics, immunology)
  • Receptors, CXCR4 (genetics, immunology, metabolism)
  • Receptors, OX40 (immunology)
  • Vesiculovirus (genetics, isolation & purification, metabolism)
  • Viral Load

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