Evans et al JGV.pdf (2.12 MB)
Antigenic site changes in the rabies virus glycoprotein dictates functionality and neutralizing capability against divergent lyssaviruses
journal contribution
posted on 2023-06-09, 11:43 authored by J S Evans, D Selden, G Wu, Edward WrightEdward Wright, D L Horton, A R Fooks, A C BanyardLyssavirus infection has a near 100?% case fatality rate following the onset of clinical disease, and current rabies vaccines confer protection against all reported phylogroup I lyssaviruses. However, there is little or no protection against more divergent lyssaviruses and so investigation into epitopes within the glycoprotein (G) that dictate a neutralizing response against divergent lyssaviruses is warranted. Importantly, the facilities required to work with these pathogens, including wild-type and mutated forms of different lyssaviruses, are scarcely available and, as such, this type of study is inherently difficult to perform. The relevance of proposed immunogenic antigenic sites within the lyssavirus glycoprotein was assessed by swapping sites between phylogroup-I and -II glycoproteins. Demonstrable intra- but limited inter-phylogroup cross-neutralization was observed. Pseudotype viruses (PTVs) presenting a phylogroup-I glycoprotein containing phylogroup-II antigenic sites (I, II III or IV) were neutralized by antibodies raised against phylogroup-II PTV with the site II (IIb, aa 34–42 and IIa, aa 198–200)-swapped PTVs being efficiently neutralized, whilst site IV-swapped PTV was poorly neutralized. Specific antibodies raised against PTV-containing antigenic site swaps between phylogroup-I and -II glycoproteins neutralized phylogroup-I PTVs efficiently, indicating an immunodominance of antigenic site II. Live lyssaviruses containing antigenic site-swapped glycoproteins were generated and indicated that specific residues within the lyssavirus glycoprotein dictate functionality and enable differential neutralizing antibody responses to lyssaviruses.
History
Publication status
- Published
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- Accepted version
Journal
Journal of General VirologyISSN
0022-1317Publisher
Microbiology SocietyExternal DOI
Volume
99Page range
169-180Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2018-01-23First Open Access (FOA) Date
2019-01-04First Compliant Deposit (FCD) Date
2018-01-22Usage metrics
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