Antibody-independent activation of the classical complement pathway by cytomegalovirus-infected fibroblasts.
Human fibroblasts weakly activated the alternative complement pathway, as assessed by C3b deposition, while 4- to 5-fold more C3b was observed 4 days after infection on cytomegalovirus (CMV)-infected fibroblasts when incubated with human serum. CMV-infected fibroblasts activated via the classical complement pathway independent of specific anti-CMV antibody and incubation of CMV-infected fibroblasts with serum deficient in complement components revealed that C1q, but not mannan-binding lectin, was required for complement activation. The enhanced complement activation by CMV-infected cells was observed as early as 4 h after infection and required the active transcription of CMV genes. No difference in the complement activation by CMV-infected cells was observed with the use of CMV-seropositive or -seronegative serum as a complement source, suggesting that CMV infection induces or up-regulates a protein that binds directly to C1q in a complement-activating conformation.
Spiller
O B
OB
Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, UK. SpillerB@Cardiff.ac.uk
Morgan
B P
BP
D001769:Blood; D002478:Cells, Cultured; D015922:Complement C1q / Q000502:physiology; D003179:Complement C3b / Q000032:analysis / Q000096:biosynthesis; D003171:Complement Pathway, Classical / Q000276:immunology / Q000502:physiology*; D003470:Culture Media; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007231:Infant, Newborn; D007700:Kinetics; D008297:Male; D012867:Skin / Q000276:immunology* / Q000821:virology; D014158:Transcription, Genetic
D003470:Culture Media; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015922:Complement C1q; D003179:Complement C3b