TY - JOUR
T1 - Identification of amino acid substitutions escaping from a broadly neutralizing monoclonal antibody of feline calicivirus
AU - Fujita, Shigeru
AU - Koba, Ryota
AU - Tohya, Yukinobu
N1 - Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/9
Y1 - 2022/9
N2 - Feline calicivirus (FCV) causes upper respiratory tract diseases in cats and has highly variable antigenicity for neutralization of each strain. Neutralizing epitopes of FCV are currently found in the hypervariable region (HVR) in the P2 domain of the major capsid protein VP1. Due to its unique ability to neutralize various FCV strains, 1D7 is a monoclonal antibody that may recognize a novel neutralizing epitope. While other neutralizing epitopes were characterized by producing neutralization-resistant variants, only 1D7-resistant variants could not be obtained, and its epitope has not been identified in the previous studies. In this study, we successfully generated these variants by multiple passaging of the FCV F4 strain in the presence of 1D7 and discovered that several amino acid substitutions (K638N, R662G, and T666I in the P1 domain of VP1) are involved in the decreased binding of 1D7. These substitution sites are also highly conserved among FCV strains compared with the substitution sites of other neutralization-resistant variants found in the HVR. Our results indicate that amino acid substitutions in the P1 domain, which are not responsible for direct interaction with the FCV receptor, are associated with neutralization escape. Since FCV can be conveniently cultured in vitro and the receptor required for infection is known, a detailed analysis of the 1D7 epitope could shed more light on the neutralization mechanism of the epitopes of viruses belonging to the Caliciviridae.
AB - Feline calicivirus (FCV) causes upper respiratory tract diseases in cats and has highly variable antigenicity for neutralization of each strain. Neutralizing epitopes of FCV are currently found in the hypervariable region (HVR) in the P2 domain of the major capsid protein VP1. Due to its unique ability to neutralize various FCV strains, 1D7 is a monoclonal antibody that may recognize a novel neutralizing epitope. While other neutralizing epitopes were characterized by producing neutralization-resistant variants, only 1D7-resistant variants could not be obtained, and its epitope has not been identified in the previous studies. In this study, we successfully generated these variants by multiple passaging of the FCV F4 strain in the presence of 1D7 and discovered that several amino acid substitutions (K638N, R662G, and T666I in the P1 domain of VP1) are involved in the decreased binding of 1D7. These substitution sites are also highly conserved among FCV strains compared with the substitution sites of other neutralization-resistant variants found in the HVR. Our results indicate that amino acid substitutions in the P1 domain, which are not responsible for direct interaction with the FCV receptor, are associated with neutralization escape. Since FCV can be conveniently cultured in vitro and the receptor required for infection is known, a detailed analysis of the 1D7 epitope could shed more light on the neutralization mechanism of the epitopes of viruses belonging to the Caliciviridae.
KW - Caliciviridae
KW - Feline calicivirus
KW - Feline calicivirus FCV
KW - Feline junctional adhesion molecule-A
KW - fJAM-A
KW - Monoclonal antibody
KW - Monoclonal antibody MAb
KW - Neutralizing epitope
UR - http://www.scopus.com/inward/record.url?scp=85132539770&partnerID=8YFLogxK
U2 - 10.1016/j.virusres.2022.198848
DO - 10.1016/j.virusres.2022.198848
M3 - Article
C2 - 35691421
AN - SCOPUS:85132539770
SN - 0168-1702
VL - 318
JO - Virus Research
JF - Virus Research
M1 - 198848
ER -