TY - JOUR
T1 - Involvement of gD/HVEM interaction in NF-kB-dependent inhibition of apoptosis by HSV-1 gD
AU - Sciortino, Maria Teresa
AU - Medici, Maria Antonietta
AU - Marino-Merlo, Francesca
AU - Zaccaria, Daniela
AU - Giuffrè-Cuculletto, Maria
AU - Venuti, Assunta
AU - Grelli, Sandro
AU - Bramanti, Placido
AU - Mastino, Antonio
PY - 2008/12/1
Y1 - 2008/12/1
N2 - In the present paper, we aimed to verify whether the interaction of the glycoprotein D (gD) of herpes simplex 1 (HSV-1) with the HSV-1 receptor HVEM is involved in NF-κB-dependent protection against apoptosis by gD. To this purpose, first we utilized MAbs that interfere with gD/HVEM interaction and U937 cells that naturally express human HVEM on their surface. Pre-incubation with these MAbs, but not with a control antibody, partially reverted the protection of infectious HSV-1 towards anti-Fas induced apoptosis in U937 cells. Similarly, pre-incubation of UV-inactivated HSV-1 (UV-HSV-1) or recombinant gD with the same MAbs, significantly reduced the inhibition of Fas-mediated apoptosis by UV-HSV-1 or gD, respectively, in U937 cells. Moreover, coculture with stable transfectants expressing at surface level wild type gD protected U937 cells against Fas-induced apoptosis, while coculture with transfectants expressing a mutated form of gD, incapable to bind HVEM, did not protect. Finally, UV-HSV-1 protected against staurosporine-induced apoptosis in U937 cells as well as in the CHO transfectants expressing human HVEM on their surface, but not in the control CHO transfectants, which did not express HVEM. These results suggest that signaling triggered by binding of gD to HVEM could represent an additional mechanism of evasion from premature apoptotic death exerted by HSV-1-gD in HVEM-expressing cells, disclosing new opportunities of cell death manipulation by using gD preparations.
AB - In the present paper, we aimed to verify whether the interaction of the glycoprotein D (gD) of herpes simplex 1 (HSV-1) with the HSV-1 receptor HVEM is involved in NF-κB-dependent protection against apoptosis by gD. To this purpose, first we utilized MAbs that interfere with gD/HVEM interaction and U937 cells that naturally express human HVEM on their surface. Pre-incubation with these MAbs, but not with a control antibody, partially reverted the protection of infectious HSV-1 towards anti-Fas induced apoptosis in U937 cells. Similarly, pre-incubation of UV-inactivated HSV-1 (UV-HSV-1) or recombinant gD with the same MAbs, significantly reduced the inhibition of Fas-mediated apoptosis by UV-HSV-1 or gD, respectively, in U937 cells. Moreover, coculture with stable transfectants expressing at surface level wild type gD protected U937 cells against Fas-induced apoptosis, while coculture with transfectants expressing a mutated form of gD, incapable to bind HVEM, did not protect. Finally, UV-HSV-1 protected against staurosporine-induced apoptosis in U937 cells as well as in the CHO transfectants expressing human HVEM on their surface, but not in the control CHO transfectants, which did not express HVEM. These results suggest that signaling triggered by binding of gD to HVEM could represent an additional mechanism of evasion from premature apoptotic death exerted by HSV-1-gD in HVEM-expressing cells, disclosing new opportunities of cell death manipulation by using gD preparations.
KW - Apoptosis
KW - Glycoprotein D
KW - HSV-1
KW - HVEM
KW - Viral evasion
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U2 - 10.1016/j.bcp.2008.07.030
DO - 10.1016/j.bcp.2008.07.030
M3 - Article
C2 - 18723002
AN - SCOPUS:55949090236
VL - 76
SP - 1522
EP - 1532
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 11
ER -