Visit our Expo - Redox and Inflammation signaling 2012

Session II : Receptor signaling and G proteins Poster II, 47
Signaling pathway utilized by HSV-1 to induce NF-kB activation: possible role of
herpesvirus entry receptor A
M. Teresa Sciortino,1 M. Antonietta Medici,1 Francesca Marino-Merlo,1 Daniela
Zaccaria,1 Maria Gioffrè,1 Assunta Venuti,1 A. Pia Camuti,1 Sandro Grelli,2 Antonio
Mastino1
1Dept. of Microbiol., Genet. and Mol. Sci., Univ. of Messina, Salita Sperone 31, 98166
Messina, Italy. E-mail: antonio.mastino@unime.it. 2Dept. of Exp. Med. and Bioch. Sci.,
Univ. of Rome “Tor Vergata”, Rome, Italy.
We have previously demonstrated that wild type herpes simplex 1 (HSV-1), as well as nonreplicating
UV-inactivated HSV-1, promptly activate the nuclear factor kappa B (NF-kB) in
U937 monocytoid cells and that glycoprotein D (gD) of HSV-1 is sufficient by itself to exert a
similar effect. We have then investigated the signaling pathway utilized by HSV-1 to initiate
NF-kB activation and, particularly, whether our observation could be related to the capability
of HSV-1-gD to directly stimulate NF-kB through its interaction with the herpesvirus entry
receptor A (HveA). Here we report that: a) exposure to UV-inactivated HSV-1 induced a
MOI-dependent activation of NF-kB in HveA expressing THP-1 monocytoid cells, b)
exposure to soluble gD induced a dose-dependent activation of NF-kB in THP-1 cells that
was inhibited by an antibody able to interfere with gD/HveA interaction, c) cocultivation of
THP-1 cells with an adherent cell line forced to express wild type gD on its surface by stable
transfection led to NF-kB activation, d) cell-to-cell contacts of THP-1 cells with the same
adherent cell line forced to express on its surface, by stable transfection, a mutated form of gD
lacking the capability to interact with HveA, did not activate NF-kB. These results suggest
that HSV-1-gD/HveA interaction is sufficient for triggering a signal transduction pathway
leading to NF-kB activation.
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