DIFFERENTIAL-EFFECTS OF CYTOMEGALOVIRUS-INFECTION ON COMPLEMENT SYNTHESIS BY HUMAN MESANGIAL CELLS

Viruses may be eliminated by the host immune system via complement-med iated lysis of infected cells. Previously, we have demonstrated that t he synthesis of complement factor B by renal mesangial cells (MC) is e nhanced by interferon-alpha (IFN-alpha), -beta and -gamma. In the pres ent study we investigate the effect of human cytomegalovirus (HCMV) in fection 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/10(6) cells per 72 h, resp ectively. In HCMV-infected MC cultures an induction of both factor B a nd C2 protein synthesis was observed up to 2.2 +/- 1.1 and 156 +/- 74 ng/10(6) cells per 72 h, respectively. The synthesis of C4 and factor H of 2.9 +/- 2.0 and 146 +/- 31 ng/10(6) cells, respectively, was not altered significantly. By Northern blot and reverse transcriptase-poly merase chain reaction (RT-PCR) analysis it was demonstrated that facto r B and C2 mRNA expression were up-regulated in HCMV-infected cell cul tures, whereas the levels of C4 and factor H mRNA were not changed. Wh en MC cultures were inoculated with heat-or UV-inactivated HCMV no enh ancement of factor B mRNA expression was observed. The enhanced expres sion was not blocked by phosphono acetic acid (PAA), suggesting that e xpression 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.