TY - JOUR
T1 - GP5 of porcine reproductive and respiratory syndrome virus (PRRSV) as a target for homologous and broadly neutralizing antibodies
AU - Popescu, Luca N.
AU - Trible, Benjamin R.
AU - Chen, Nanhua
AU - Rowland, Raymond R.R.
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/9
Y1 - 2017/9
N2 - 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).
AB - 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).
KW - Broadly neutralizing antibodies
KW - HCV
KW - Neutralizing epitopes
KW - PRRS
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U2 - 10.1016/j.vetmic.2017.04.016
DO - 10.1016/j.vetmic.2017.04.016
M3 - Review article
C2 - 28528961
AN - SCOPUS:85019853036
SN - 0378-1135
VL - 209
SP - 90
EP - 96
JO - Veterinary Microbiology
JF - Veterinary Microbiology
ER -