Glycoprotein C of herpes simplex virus type 1 is essential for the virus to evade antibody-independent complement-mediated virus inactivation and lysis of virus-infected cells

Abstract

Glycoprotein C (gC) of herpes simplex virus type 1 (HSV-1) is a receptor for the complement component C3b. We have previously isolated HSV-1 gC-strains (TN1, TN2 and TN3) from a patient with recurrent keratitis at three different times. These are very rare isolates because gC was thought to be essential for the virus in vivo. To determine whether gC modifies the interaction of complement with cell-free virus or virusinfected cells, we constructed gC + recombinant viruses in which the intact gC gene of strain KOS was inserted into the TN 1 virus genome. TN 1 virus was inactivated by complement and TN1 virus-infected cells were lysed by complement; however, gC ÷ recombinant viruses became resistant to these effects of complement. These results suggest a role for gC in protection of both the virion envelope and the infected cell surface against damage by complement. TN1 virus was inactivated by complement from rats (Wistar, WKA, F344 and SD), guinea-pigs (Hartley) and humans, but not by complement from mice (C3H, DDD and BALB/c), which indicates that mice seem to be inappropriate as an experimental model for the study of HSV infection in which complement factors need to be considered.

Cloning and expression of the complement receptor glycoprotein C from Herpesvirus simiae (herpes B virus): protection from complement-mediated cell lysis

“…gC HSV-1 was found to be very similar to known human complement regulatory proteins, thus competing for binding with the alternative pathway activator properdin or regulator protein factor H, which was not observed using purified gC HSV-2 (Huemer et al, 1993b). Absence of gC HSV-1 or pseudorabies virus (PRV) gIII (gC PRV ) on virions has been shown to cause increased virus lysis via the alternative complement pathway and interestingly, species variations in the efficiency of lysis using different complement sources have been observed (Hidaka et al, 1991;Ikeda et al, 2000;Maeda et al, 2002). This is in accordance with the finding of differences in the binding to complement C3 of herpesvirus gC proteins of different species (Huemer et al, 1993a).…”

“…Certain species-specific selectivity is observed among human complement regulators (Horstmann et al, 1985;Yu et al, 1997) and marked differences in the efficiency of complement-mediated herpesvirus lysis using serum of different species as a complement source have been described (Hidaka et al, 1991;Maeda et al, 2002). The findings that HSV was lysed far more efficiently by serum of rodents as compared to human serum than earlier reports have suggested appears to play a crucial role in animal studies using herpesvirus vectors for anti-tumour therapy (Ikeda et al, 2000).…”

Species selective interaction of Alphaherpesvirinae with the “unspecific” immune system of the host

“…However, in vitro HSVinfected cells are rather resistant to complement lysis in the absence of antibody [15,38]. This seems to be due to the function of HSV glycoprotein gC which interacts with C 3, the pivotal component of the complement cascade [7,9,28], and thereby inhibits alternative pathway complement activation [11,15,17].…”

Stromal Keratitis Induced by a Unique Clinical Isolate of Herpes simplex Virus Type 1

“…RTN-1-20-3 [11] and C-3 [12] arc gC-positive re combinant viruses derived from TN-1. Following intracerebral inoc ulation in mice, the virulence of RTN-1-20-3 was comparable to that ofTN -l [11],…”