The carboxy-terminal half of nonstructural protein 3A is not essential for foot-and-mouth disease virus replication in cultured cell lines

Mrutyunjay Behura, Jajati K. Mohapatra, Laxmi K. Pandey, Biswajit Das, Mukesh Bhatt, Saravanan Subramaniam, Bramhadev Pattnaik

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

In foot-and-mouth disease (FMD)-endemic parts of the globe, control is mainly implemented by preventive vaccination with an inactivated purified vaccine. ELISAs detecting antibodies to the viral nonstructural proteins (NSP) distinguish FMD virus (FMDV)-infected animals in the vaccinated population (DIVA). However, residual NSPs present in the vaccines are suspected to be a cause of occasional false positive results, and therefore, an epitope-deleted negative marker vaccine strategy is considered a more logical option. In this study, employing a serotype Asia 1 FMDV infectious cDNA clone, it is demonstrated that while large deletions differing in size and location in the carboxy-terminal half of 3A downstream of the putative hydrophobic membrane-binding domain (deletion of residues 86-110, 101-149, 81-149 and 81-153) are tolerated by the virus without affecting its infectivity in cultured cell lines, deletions in the amino-terminal half (residues 5-54, 21-50, 21-80, 55-80 and 5-149) containing the dimerization and the transmembrane domains are deleterious to its multiplication. Most importantly, the virus could dispense with the entire carboxy-terminal half of 3A (residues 81-153) including the residues involved in the formation of the 3A-3B1 cleavage junction. The rescue of a replication-competent FMDV variant carrying the largest deletion ever in 3A (residues 81-153) and the fact that the deleted region contains a series of linear B-cell epitopes inspired us to devise an indirect ELISA based on a recombinant 3A carboxy-terminal fragment and to evaluate its potential to serve as a companion diagnostic assay for differential serosurveillance if the 3A-truncated virus is used as a marker vaccine.

Original languageEnglish
Pages (from-to)1295-1305
Number of pages11
JournalArchives of Virology
Volume161
Issue number5
DOIs
StatePublished - 1 May 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016, Springer-Verlag Wien.

Funding

Acknowledgments This study was funded by the Indian Council of Agricultural Research.

FundersFunder number
Indian Council of Agricultural Research

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