Influence of Foot-and-Mouth Disease Virus O/CHN/Mya98/33-P Strain Leader Protein on Viral Replication and Host Innate Immunity

Abstract

Foot-and-mouth disease virus (FMDV) O/CHN/Mya98/33-P strain was isolated from the esophageal-pharyngeal fluid sample of cattle, and was shown to cause persistent infection. Its leader protein contains 200 amino acids with one amino acid deletion, which is upstream and next to the second initiation codon compared with the majority of FMDV Mya98 strains. The FMDV genome includes two initiation codons that can produce two different leader proteins, Lab (from the first AUG) and Lb (from the second AUG). For convenience, the inter-AUG region was named as La. Previously, it was found that a recombinant virus with Lab of FMDV O/CHN/Mya98/33-P strain had higher proliferation efficiency, and better ability to inhibit the host innate immune response. Three full-length infectious cDNA clones-rHN33-Lb, rHN33-La, and rHNGSLX-Lb-containing the FMDV O/CHN/Mya98/33-P strain leader proteins Lb, La, or the FMDV O/GSLX/2010 strain leader protein Lb, respectively, were constructed based on an established infectious clone r-HN rescued from FMDV O/HN/CHN/93 strain. After infecting pig kidney primary cells, rHN33-La showed higher replication efficiency than r-HN, and rHN33-Lb displayed better ability to resist host innate immunity than rHNGSLX-Lb. These results demonstrated that the inter-AUG region of FMDV strain O/CHN/Mya98/33-P leader protein must be involved in increasing viral replication efficiency. Additionally, the Lb of FMDV O/CHN/Mya98/33-P must be involve in increasing its ability to inhibit host innate immune response, and the distinctive amino acids G56 and/or R118 of FMDV leader protein may play essential roles in it.

Foot-and-Mouth Disease Virus: Immunobiology, Advances in Vaccines and Vaccination Strategies Addressing Vaccine Failures—An Indian Perspective

“…Workers have created modified viruses by mutating deleterious genes, altering replication fidelity, and deoptimizing codons, and these demonstrated protection in animals with variable degrees of success [60]. Modification in the leader protein of FMDV or by changing one of the two translation initiation sites in the virus has been demonstrated, though studies in animals are limited [56,60,61,62,63,64]. It was demonstrated that RNAs carrying the deletion of the stem loop in the 3′ UTR on a serotype-O FMDV genome were innocuous when inoculated in pigs but elicited specific humoral and cellular immune responses [65].…”

Deciphering Molecular Dynamics of Foot and Mouth Disease Virus (FMDV): A Looming Threat to Pakistan’s Dairy Industry

“…Extraneous cofactors also contribute to RGD attachment, e.g., both FMDV attachment to cells and integrin receptor activity are dependent on divalent cations [40], and there is evidence that disialogangliosides contribute to the attachment of melanoma cells to RGD-containing substrates [28]. Amino acids of the VP2 region (1-33) are also capable of producing antibody response elicited by the VP1 region, but it is weakly immunogenic because the N-terminus of the VP2 protein is positioned at the bottom of the three-fold symmetry axis of the virus protein coat [43].…”