Mechanisms of bovine herpesvirus type 1 neutralization by monoclonal antibodies to glycoproteins gI, gIII and gIV.

We examined a panel of monoclonal antibodies (MAbs) against bovine herpesvirus type 1 (BHV-1) glycoproteins gI, gIII and gIV for inhibition of virus attachment and interference with subsequent steps of infection. Attachment of radiolabelled virions was partially prevented by 600 to 700 micrograms/ml of IgM antibodies against gI and gIII and one IgG2A antibody against gIV, but not by the majority of MAbs against any of the three viral glycoproteins. Productive infection following attachment was prevented by lower concentrations of MAbs 5106 and 4807 against gI and by 0.7 to 5.5 micrograms/ml of all five MAbs against gIV. MAbs against gIV had almost the same activity whether added before or after BHV-1 was incubated with cells, suggesting that their principal activity is to prevent the penetration of virus through the cell membrane. The ability of polyethylene glycol to overcome neutralization by one anti-gIV MAb supported this concept, but an attempt to confirm this by direct electron microscopy failed. A bovine monospecific antiserum against gIV had approximately 10-fold more neutralizing activity against BHV-1 than did antisera against gI or gIII. Complement increased the activity of anti-gI and anti-gIII MAbs by 10- to 100-fold, but had little or no effect on neutralization by anti-gIV MAbs. Some antibodies against gI and gIV inhibited the enlargement of plaques in cell cultures. Taken together, these data suggest that MAbs against gIV are the principal agents of BHV-1 neutralization, and that these antibodies can be fully effective in areas such as the ocular and respiratory mucosae, from which complement is absent at the time of primary exposure to infection.