Location of, immunogenicity of and relationships between neutralization epitopes on the attachment protein (G) of Hendra virus.
Epitopes involved in a protective immune response to Hendra virus (HeV) (Henipavirus, Paramxyoviridae) were investigated by generating five neutralizing monoclonal antibodies (mAbs) to the virus attachment protein (G) of HeV (HeV G) and sequencing of the G gene of groups of neutralization-escape variants selected with each mAb. Amino acid substitutions occurred at eight distinct sites on HeV G. Relationships between these sites were investigated in binding and neutralization assays using heterologous combinations of variants and mAbs. The sites were also mapped to a proposed structural model for the attachment proteins of Paramyxoviridae. Their specific locations and the nature of their interactions with the mAb panel provided the first functional evidence that HeV G in fact resembled the proposed structure. Four sites (aa 183-185, 417, 447 and 570) contributed to a major discontinuous epitope, on the base of the globular head, that was similar to immunodominant virus neutralization sites found in other paramyxoviruses. Amino acid similarity between HeV and Nipah virus was relatively highly conserved at these sites but decreased significantly at the other sites identified in this study. These included another discontinuous epitope on the base of the head region defined by sites aa 289 and 324 and well separated epitopes on the top of the head at sites aa 191-195 and 385-356. The latter epitope corresponded to immunodominant neutralization sites found in Rinderpest virus and Measles virus.
White
John R
JR
CSIRO Division of Livestock Industries, Australian Animal Health Laboratory, Geelong, VIC 3220, Australia.
Boyd
Victoria
V
CSIRO Division of Livestock Industries, Australian Animal Health Laboratory, Geelong, VIC 3220, Australia.
Crameri
Gary S
GS
CSIRO Division of Livestock Industries, Australian Animal Health Laboratory, Geelong, VIC 3220, Australia.
Duch
Christine J
CJ
CSIRO Division of Livestock Industries, Australian Animal Health Laboratory, Geelong, VIC 3220, Australia.
van Laar
Ryan K
RK
CSIRO Division of Livestock Industries, Australian Animal Health Laboratory, Geelong, VIC 3220, Australia.
Wang
Lin-Fa
LF
CSIRO Division of Livestock Industries, Australian Animal Health Laboratory, Geelong, VIC 3220, Australia.
Eaton
Bryan T
BT
CSIRO Division of Livestock Industries, Australian Animal Health Laboratory, Geelong, VIC 3220, Australia.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D045404:Hendra Virus / Q000145:classification / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D014759:Viral Envelope Proteins; C116204:attachment protein G