Apoptosis of human peripheral blood mononuclear cells by wild-type measles virus infection is induced by interaction of hemagglutinin protein and cellular receptor, SLAM via caspase-dependent pathway.
Although MV infection causes lymphopenia and degradation of cell-mediated immunity, the mechanisms are poorly known. MV interacts with cellular receptors which mediate virus binding and uptake and are on the surface of PBMC. In this study, apoptosis of MV-infected PBMC in vitro was analyzed. Both PBMC treated with UV-inactivated viruses and those infected with live MV underwent apoptosis. Apoptosis of wild-type MV-infected PBMC was blocked by anti-SLAM and anti-MV hemagglutinin antibodies, respectively. Furthermore, addition of soluble MV hemagglutinin recombinant protein induced apoptosis in PBMC. These data suggest that induction of apoptosis in MV-infected PBMC is triggered by interaction between hemagglutinin protein of MV and receptor, without other viral components. To further determine the mechanisms of apoptosis, caspase activity was analyzed by Western blotting. Wild-type virus Yonekawa strain-induced apoptosis was blocked by pretreatment with pan-caspase inhibitor (Z-VAD-fmk). Intriguingly, the laboratory-adapted Nagahata strain-induced apoptosis was not blocked by Z-VAD-fmk, indicating that there may be different apoptosis pathways which depend on the viral receptors, SLAM and CD46. Both extrinsic and intrinsic apoptotic pathways, including activation of caspase-3, -8 and -9, are involved in Yonekawa strain-induced apoptosis. Taken together, the findings of this study could open up a new avenue for understanding the molecular mechanisms of MV-induced PBMC apoptosis and immunosuppression.
Iwasa
Tadashi
T
Department of Pediatrics, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Suga
Shigeru
S
Qi
Lei
L
Komada
Yoshihiro
Y
D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D006389:Hemagglutinins, Viral / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism / Q000821:virology; D008457:Measles / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D008459:Measles virus / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
D015703:Antigens, CD; D006389:Hemagglutinins, Viral; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D020169:Caspases