Bovine rhinitis B virus (BRBV) shares many motifs and sequence similarities with foot-and-mouth disease virus (FMDV). This study examined if the BRBV leader proteinase (Lpro ) could functionally replace that of FMDV. A mutant A24LBRV3DYR FMDV engineered with the BRBV Lpro and an antigenic marker in the 3D polymerase exhibited growth properties and eIF4G cleavage similar to parental A24WT virus. The A24LBRV3DYR type I interferon activity in infected bovine cells resembled that of A24LL virus that lacks Lpro, but this effect was less pronounced for A24LBRV3DYR infected porcine cells. In vivo studies showed that the A24LBRV3DYR virus was attenuated in cattle, and exhibited low virulence in pigs exposed by direct contact. The mutant virus induced protective immunity in cattle against challenge with parental A24WT. These results provide evidence that Lpro of different Aphthoviruses are not fully functionally interchangeable and have roles that may depend on the nature of the infected host.
Bibliographical noteFunding Information:
We thank Dr. Alfonso Clavijo for the gift of mAbs against the FMDV 3D pol and Drs. Marvin Grubman and Paul Lawrence for fruitful discussions. This research was supported by CRIS Project no. 1940-32000-053-00D , 1940-32000-057-00D , Agricultural Research Service (ARS), U.S. Department of Agriculture (Dr. Elizabeth Rieder). Dr. Sabena Uddowla, Dr. Devendra K. Rai and Mr. Christopher Larson were the recipient of a fellowship by the Plum Island Animal Disease Research Participation Program administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Department of Agriculture.
- Bovine rhinitis B virus (BRBV) leader proteinase
- Chimeric foot-and-mouth disease virus (FMDV)
- FMDV pathogenesis