GP5 of porcine reproductive and respiratory syndrome virus (PRRSV) as a target for homologous and broadly neutralizing antibodies

Virus neutralization (VN) responses range from narrowly focused antibodies with only homologous neutralizing activity against the virus used for infection, to antibodies that can neutralize both Type 1 and Type 2 viruses, referred to as broadly neutralizing antibody (bnAb). Even though neutralizing epitopes are likely distributed among several structural glycoproteins, this paper focuses on the ectodomain region of GP5 as a model system for investigating the role for neutralizing and non-neutralizing antibodies in protection and disease. Epitope B within GP5 possesses several features common to broadly neutralizing epitopes. In the proposed model, accessibility of antibody to Epitope B is blocked by homologous neutralizing and non-neutralizing antibodies, which bind flanking hypervariable domains. Additional mechanisms for blocking the accessibility of bnAb include conformational alterations within the GP5-M heterodimer and glycan shielding. This model explains how the continuous escape from homologous neutralization provides a mechanism for persistence. The proposed mechanism for immune evasion is not unique to PRRSV, but can be found in other persistent viruses, such as hepatitis C virus (HCV).