Hp. Huemer et al., HERPES-SIMPLEX VIRUS GLYCOPROTEIN-C - MOLECULAR MIMICRY OF COMPLEMENTREGULATORY PROTEINS BY A VIRAL PROTEIN, Immunology, 79(4), 1993, pp. 639-647
Herpes simplex virus (HSV) encodes a protein, glycoprotein C (gC), whi
ch binds to the third complement component, the central mediator of co
mplement activation. In this study the structural and functional relat
ionships of gC from HSV type 1 (HSV-1) and known human complement regu
latory proteins factor H, properdin, factor B, complement receptor 1 (
CR1) and 2 (CR2) were investigated. The interaction of gC with C3b was
studied using purified complement components, synthetic peptides, ant
isera against different C3 fragments and anti-C3 monoclonal antibodies
(mAb) with known inhibitory effects on C3-ligand interactions. All th
e mAb that inhibited gC/C3b interactions, in a differential manner, al
so prevented binding of C3 fragments to factors H, B, CR1 or CR2. No b
locking was observed with synthetic peptides representing different C3
regions or with factor B and C3d, whereas C3b, C3c and factor H were
inhibitory, as well as purified gC. There was no binding of gC to cobr
a venom factor (CVF), a C3c-like fragment derived from cobra gland. Pu
rified gC bound to iC3, iC3b and C3c, but failed to bind to C3d. Glyco
protein C bound only weakly to iC3 derived from bovine and porcine pla
sma, thus indicating a preference of the viral protein for the appropr
iate host. Binding of gC was also observed to proteolytic C3 fragments
, especially to the beta-chain, thus suggesting the importance of the
C3 region as a binding site. Purified gC from HSV-1, but not HSV-2, in
hibited the binding of factor H and properdin but not of CR1 to C3b. T
he binding of iC3b to CR2, a molecule involved in B-cell activation an
d binding of the Epstein-Barr virus, was also inhibited by the HSV-1 p
rotein. As factor H and properdin, the binding of which was inhibited
by gC, are important regulators of the alternative complement pathway,
these data further support a role of gC in the evasion of HSV from a
major first-line host defence mechanism, i.e. the complement system. I
n addition, the inhibition of the C3/CR2 interaction may suggest a pos
sible immunoregulatory role of HSV glycoprotein C.