Differential effects of cytomegalovirus infection on complement synthesis by human mesangial cells

• Published in: Clinical and experimental immunology Vol. 109; no. 3; pp. 518 - 525
• Main Authors: TIMMERMAN, J. J., BEERSMA, M. F. C., VAN GIJLSWIJK‐JANSSEN, D. J., VAN ES, L. A., VAN DER WOUDE, F. J., DAHA, M. R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.1997; Blackwell; Blackwell Science Inc
• Subjects: Biological and medical sciences; Blotting, Northern; Cells, Cultured; complement; Complement C2 - metabolism; Complement C4 - metabolism; Complement Factor B - metabolism; Complement Factor H - metabolism; Complement System Proteins - metabolism; Cytomegalovirus - radiation effects; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - metabolism; Fundamental and applied biological sciences. Psychology; Glomerular Mesangium - cytology; human cytomegalovirus; Humans; interferons; Interferons - pharmacology; kidney; mesangial cells; Microbiology; Original; Phosphonoacetic Acid - pharmacology; Polymerase Chain Reaction; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; RNA, Messenger - analysis; RNA, Messenger - metabolism; Ultraviolet Rays; Up-Regulation; Virology; Human; Mesangial cell; Complement C2; Alternative pathway complement; Herpesviridae; Complement C4; Cytokine; Actins; Betaherpesvirinae; In vitro; Kidney; Human cytomegalovirus; Virus; Classical pathway complement; Renal glomerulus; H Factor; Urinary system; Modulation; Interferon; Infected cell
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.1997.4651364.x

Viruses may be eliminated by the host immune system via complement‐mediated lysis of infected cells. Previously, we have demonstrated that the synthesis of complement factor B by renal mesangial cells (MC) is enhanced by interferon‐alpha (IFN‐α), ‐β and ‐γ. In the present study we investigate the effect of human cytomegalovirus (HCMV) infection on the production of complement factors by MC. The production of factor B, C2, C4 and factor H by mock‐infected MC was 0.2 ± 0.4, 3.9 ± 6.8, 1.7 ± 0.8 and 149 ± 36 ng/106 cells per 72 h, respectively. In HCMV‐infected MC cultures an induction of both factor B and C2 protein synthesis was observed up to 2.2 ± 1.1 and 156 ± 74 ng/106 cells per 72 h, respectively. The synthesis of C4 and factor H of 2.9 ± 2.0 and 146 ± 31 ng/106 cells, respectively, was not altered significantly. By Northern blot and reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis it was demonstrated that factor B and C2 mRNA expression were up‐regulated in HCMV‐infected cell cultures, whereas the levels of C4 and factor H mRNA were not changed. When MC cultures were inoculated with heat‐ or UV‐inactivated HCMV no enhancement of factor B mRNA expression was observed. The enhanced expression was not blocked by phosphono acetic acid (PAA), suggesting that expression of the HCMV immediate early or early genes is sufficient to induce complement synthesis. We conclude that infection of MC cultures with HCMV selectively induces complement C2 and factor B production, probably mediated by interferons.