A recombinant vesicular stomatitis virus encoding HIV-1 receptors and human OX40 ligand efficiently eliminates HIV-1-infected CD4-positive T cells expressing OX40.
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.
Department of Safety Research on Blood and Biological products, National Institute of Infectious Diseases, Tokyo, Japan.
Chikayuki
C
Tsuruno
Kazu
K
Okuma
Yoshiaki
Y
Takahashi
Reiko
R
Tanaka
Yuetsu
Y
Tanaka
Youichi
Y
Takahama
Yukio
Y
Hamaguchi
Isao
I
Hamaguchi
Kazunari
K
Yamaguchi
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002460:Cell Line; D045744:Cell Line, Tumor; D006224:Cricetinae; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D015726:Giant Cells / Q000378:metabolism / Q000473:pathology; D057809:HEK293 Cells; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D053278:OX40 Ligand / Q000235:genetics / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053262:Receptors, OX40 / Q000276:immunology*; D018116:Vesiculovirus / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D019562:Viral Load
D015704:CD4 Antigens; D053278:OX40 Ligand; D019718:Receptors, CXCR4; D053262:Receptors, OX40