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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #80843
Title: MAPPING OF A TYPE 1-SPECIFIC AND A TYPE COMMON EPITOPE ON THE E2 (GP53) PROTEIN OF BOVINE VIRAL DIARRHEA VIRUS WITH NEUTRALIZATION ESCAPE MUTANTS

Author
item DEREGT, D - ANIM DIS RES INST, CANADA
item Bolin, Steven - Steve
item VAN DEN HURK, J - BIOSTAR, INC., CANADA
item Ridpath, Julia
item GILBERT, S - ANIM DIS RES INST, CANADA

Submitted to: Virus Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/22/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: Bovine viral diarrhea virus (BVDV) is an economically important, widespread, disease-inducing virus of cattle. The virus infects cattle of all ages and causes pneumonia, diarrhea, abortion, and death. The virus mutates rapidly and is able to change its surface proteins to evade the animal's immune response. One of the viral surface proteins, termed E2, is san important target for the animal's immune response. Antibody produced b cattle against E2 can destroy the virus. Several naturally occurring BVDV that had mutations in E2 were identified in populations of virus that were isolated originally from diseased cattle. Those viruses were studied using monoclonal antibodies that react with small, highly specific sites on E2. By doing this, two antibody binding sites were identified on E2. Further, we found that single point mutations in the viral genetic material allowed the virus to escape the antibody. This is an important step in determining ghow BVDV persists in cattle populations. Continued studies of this type will lead to a map of antibody binding sites on E2 and provide information on the possible mutations in the viral genetic material that affect the antibody binding sites. This information is needed to design vaccines that are effective against BVDV. The immediate beneficiaries of those vaccines will be cattle producers, but ultimately consumers of beef will benefit from healthier cattle.

Technical Abstract: Bovine viral diarrhea viruses (BVDV) have recently been segregated into two genotypes, BVDV 1 and BVDV 2. However, the antigenic differences and similarities of BVDV 1 and BVDV 2 remain poorly defined. In this study, the E2 epitopes of two neutralizing monoclonal antibodies (mAbs) produced against an isolate of BVDV 1 were mapped. The mAb 157 is BVDV 1-specific, whereas mAb 348 bound to and neutralized BVDV 2. Both mAbs bound to epitopes within the first 192 amino acids of the E2 protein as determined by reactions with a C-terminally truncated E2. To identify critical amino acids affecting these epitopes, mAb escape mutants from BVDV 1 and BVDV 2 strains with different (wild-type) mAb binding phenotypes were sequenced. In addition, the E2 gene of several BVDV were sequenced and the sequences were compared with amino acid changes in mutant viruses. Single nucleotide changes in escape mutants of mAb 157 resulted in amino acid changes at E2 positions 9, 32, or 72. Amino acid changes at position 72 also affected the epitope of mAb 348. Alignment of E2 nucleotide sequences revealed that BVDV 2 are missing six nucleotides encoding the equivalent of amino acids 31 and 32 of BVDV 1 and thus this difference can account for the BVDV 1-spe ity of mAb 157. Single nucleotide mutations in mAb 348 escape mutants of BVDV 1 and BVDV 2 resulted in changes in 3 amino acids in the previously described immunodominant 71-74 region (Virology 190, 763-772). A fourth amino acid change observed in a mutant of BVDV 2 extended this region to position 77. Thus, the amino acid changes affecting the conserved epitope of mAb 348 occurred in a short spatial array over only 7 amino acids, unlike the described composite epitopes previously mapped to this region.