Specificities of monoclonal and polyclonal antibodies that inhibit adsorption of herpes simplex virus to cells and lack of inhibition by potent neutralizing antibodies

Abstract

Polyclonal and monoclonal antibodies to individual herpes simplex virus (HSV) glycoproteins were tested for ability to inhibit adsorption of radiolabeled HSV type 1 (HSV-1) strain HFEMsyn [HSV-1(HFEM)syn] to HEp-2 cell monolayers. Polyclonal rabbit antibodies specific for glycoprotein D (gD) or gC and three monoclonal mouse antibodies specific for gD-l or gC-1 most effectively inhibited HSV-1 adsorption. Antibodies of other specificities had less or no inhibitory activity despite demonstrable binding of the antibodies to virions. Nonimmune rabbit immunoglobulin G and Fc fragments partially inhibited adsorption when used at relatively high concentrations. These results suggest involvement of gD, gC, and perhaps gE (the Fc-binding glycoprotein) in adsorption. The monoclonal anti-gD antibodies that were most effective at inhibiting HSV-1 adsorption had only weak neutralizing activity. The most potent anti-gD neutralizing antibodies had little effect on adsorption at concentrations significantly higher than those required for neutralization. This suggests that, although some anti-gD antibodies can neutralize virus by blocking adsorption, a more important mechanism of neutralization by anti-gD antibodies may be interference with a step subsequent to adsorption, possibly penetration.

Mechanisms of transmissible gastroenteritis coronavirus neutralization

“…These results strongly suggest that both infectious and noninfectious virions have a functional spike protein mediating the binding of the virus to the cells . The limitations derived from the inhability to follow isolated infectious virions have been accepted in all the studies analyzing the interaction between viruses and cells, by electron microscopy or using radiolabeled virions (Fuller and Spear, 1985 ;FulleretaL, 1989 ;Highlander et al, 1987 ;Miller and Hutt-Fletcher, 1988) . In all cases, the observed virions, or most of the radioactivity, corresponds to noninfectious particles .…”

“…Similarly, influenza virus neutralized by saturating amounts of monoclonal IgG directed against the hemagglutinin enters the cells and undergoes primary but not secondary uncoating in vivo (Rigg et al, 1989) . In the herpes simplex virus system, MAbs have been described with potent neutralizing activity not associated with the inhibition of virus adsorption but with the inhibition of internalization (Fuller and Spear, 1985 ;Fulleretal., 1989) .…”

Inhibitors of protein glycosylation and glycoprotein processing in viral systems

“…However, the rapid cytolytic infection of HSV in infected cultured cells has enabled detailed studies on all phases of the infectious cycle. * The infection is initiated by the binding between one or more glycoproteins in the viral envelope and receptors in the permissive cell (Svennerholm, personal communication;Fuller and Spear, 1985). HSV type 1 (HSV-1), which is causing predominantly oral-facial infections, binds to other receptors than HSV-2, mainly associated with genital herpes (Vahlne et al, 1979).…”

“…HSV-glycoproteins contain N-linked oligosaccharides of the complex-type and the high rnannose type, the high-mannose oligosaccharides being associated mainly with partially- Fuller and Spear, 1985); (5) Svennerholm, B., Jeansson, S., Vahlne, A. and Lycke, E., submitted (6) Olofsson et al, 1981a,b: (7) Olofsson et al, 1983;(8) Baucke and Spear, 1979;(9) Spear, 1985;(10) Noble et al, 1983;(11) Serafini-Cessi et al, 1985;(12) Olofsson et al, 1986;(13) Buckmaster et al, 1984;(14) Johnson and Spear, 1983;(15) Little et al, 1981. Abbreviations: HPA, Helix pomatia lectin. processed glycoprotein precursors detected in the infected cell.…”

“…Both the adsorption and penetration process of HSV each seem to be mediated by more than one glycoprotein (Svennerholm, personal communication;Fuller and Spear, 1985;Noble et al, 1983). Undoubtedly, gC plays an important role as a virus-absorption protein because the adsorption of HSV to permissive cells can be blocked by some monoclonal gC-specific antibodies (Fuller and Spear, 1985;Svennerholm, personal communication). However, as gC-negative HSV strains have the ability to adsorb and productively infect permissive cells, there must be at least one more glycoprotein in the HSV envelope with the ability to initiate attachment.…”