Induction of interferon-alpha by glycoprotein D of herpes simplex virus: a possible role of chemokine receptors.
The induction of type I interferons by most RNA viruses is initiated by virus-derived double-stranded (ds)RNA. However, retro- and DNA-viruses, which do not synthesize dsRNA, must rely on different mechanisms of induction. For human immunodeficiency virus type 1 (HIV-1), recombinant glycoproteins 120 or 160 suffice to induce interferon (IFN)-alpha in blood-derived lymphocytes [H. Ankel, M. R. Capobianchi, C. Castilletti, and F. Dianzani (1994). Virology 205, 34-43]. Here we show that for herpes simplex virus type 1 (HSV-1) recombinant glycoprotein, gD is the major inducer, whereas gB, gC, gE, gG, gI, and the complex of gH and gL are poor inducers. The recombinant extramembrane fragment of gD was sufficient to induce IFN-alpha levels comparable to that of intact virus. Like with HIV-1, induction was inhibited by a monoclonal antibody that recognizes cerebrosides and sulfatides. Furthermore, monoclonal antibodies specific for the chemokine receptors CCR3 and CXCR4 also blocked induction. We conclude that HSV-1 induces IFN-alpha by interaction of its glycoprotein gD with appropriate receptors on IFN-producing cells. Based on the known receptor roles of galactosyl cerebrosides and chemokine receptors in HIV infection, such structures on IFN-producing cells could also participate in the induction of IFN-alpha by HSV-1.
Ankel
H
H
Hôpital Saint-Vincent-de-Paul, Faculté de Médecine Cochin-Port-Royal, Université René-Descartes, 82 Avenue Denfert-Rochereau, Paris, 75014, France. hankel@infobiogen.fr
Westra
D F
DF
Welling-Wester
S
S
Lebon
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000914:Antibodies, Viral / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006389:Hemagglutinins, Viral / Q000276:immunology / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D054397:Receptors, CCR3; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D018411:Spodoptera; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; C515350:CCR3 protein, human; D006389:Hemagglutinins, Viral; D016898:Interferon-alpha; D054397:Receptors, CCR3; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1