Epstein-Barr virus regulates activation and processing of the third component of complement.
Serum incubated with purified EBV was found to contain C3 cleavage fragments characteristic of C3c. Since the cofactors necessary for such cleavage of C3b by factor I are not normally present in serum, EBV was tested for factor I cofactor activity. Purified EBV from both human and marmoset EBV-producing cell lines was found to act as a cofactor for the factor I-mediated breakdown C3b to iC3b and iC3b to C3c and C3dg. EBV also acted as a cofactor for the factor I-mediated cleavage of C4b to iC4b and iC4b to C4c and C4d. EBV from both the human and marmoset cell lines accelerated the decay of the alternative pathway C3 convertase. The classical pathway C3 convertase was unaffected. Multiple lines of evidence eliminated the possibility that marmoset or human CR1 was responsible for the functional activities of EBV preparations. The spectrum of activities was different from CR1 in that EBV and EBV-expressing cell lines failed to rosette with C3b or particles bearing C3b, the primary functional assay for CR1, and EBV did not accelerate classical pathway C3 convertase decay, another property of CR1. In addition, CR1 could not be detected immunologically on marmoset or human EBV-expressing cells and mAbs to CR1 failed to alter EBV-produced decay acceleration and factor I cofactor activities, although the antibodies blocked the same CR1-dependent functional activities. The multiple complement regulatory activities exhibited by purified EBV derived from human and marmoset cells differ from those of any of the known C3 or C4 regulatory proteins. These various activities would be anticipated to provide survival value for the virus by subverting complement- and cell-dependent host defense mechanisms.
Mold
C
C
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Bradt
B M
BM
Nemerow
G R
GR
Cooper
N R
NR
D000818:Animals; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism*; D003179:Complement C3b / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D015935:Complement C4b; D017244:Complement Factor I; D006566:Herpesviridae Infections / Q000503:physiopathology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D011485:Protein Binding; D011951:Receptors, Complement / Q000378:metabolism; D017463:Receptors, Complement 3b; D012697:Serine Endopeptidases / Q000378:metabolism
D003176:Complement C3; D003181:Complement C4; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D003179:Complement C3b; D015935:Complement C4b; D012697:Serine Endopeptidases; D017244:Complement Factor I