Signaling pathway used by HSV-1 to induce NF-kappaB activation: possible role of herpes virus entry receptor A.
We have previously demonstrated that wild-type herpes simplex virus type 1 (HSV-1), as well as nonreplicating UV-inactivated HSV-1, promptly activates the nuclear factor-kappaB (NF-kappaB) in U937 monocytoid cells and that glycoprotein D (gD) of HSV-1 is sufficient by itself to exert a similar effect. We then investigated the signaling pathway used by HSV-1 to initiate NF-kappaB activation and, particularly, whether our observation could be related to the capability of HSV-1-gD to directly stimulate NF-kappaB through its interaction with the herpes virus entry receptor A (HveA). Here we report that: (a) co-cultivation of U937 cells with an adherent cell line expressing wild-type gD on its surface led to increased NF-kappaB activation, while co-cultivation with the same adherent cell line expressing a mutated form of gD, lacking the capability to bind HveA, did not cause the same effect; (b) exposure to UV-inactivated HSV-1 induced the activation of NF-kappaB in HveA-expressing U937 and THP-1 cells, but not in non-HveA-expressing HEp-2 cells; and (c) activation of NF-kappaB in U937 and THP-1 cells exposed to soluble gD was inhibited by an antibody able to interfere with gD-HveA interaction. These results suggest that HSV-1-gD-HveA interaction initiates a signal transduction pathway leading to NF-kappaB activation.
Teresa Sciortino
M
M
Department of Microbiological, Genetic, and Molecular Sciences, University of Messina, Salita Sperone 31, 98166 Messina, Italy.
Medici
M Antonietta
MA
Marino-Merlo
Francesca
F
Zaccaria
Daniela
D
Giuffrè
Maria
M
Venuti
Assunta
A
Grelli
Sandro
S
Mastino
Antonio
A
D002448:Cell Adhesion; D002460:Cell Line; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D020298:U937 Cells; D014759:Viral Envelope Proteins / Q000378:metabolism
D016328:NF-kappa B; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506028:TNFRSF14 protein, human; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1