Identification of BVDV2b and 2c subgenotypes in the United States: genetic and antigenic characterization

Authors: Neill, John; Workman, Aspen; HESSE, RICHARD - Kansas State University; BAI, JIANFA - Kansas State University; POULSEN-PORTER, ELIZABETH - Kansas State University; MEADORS, BARBARA - Kansas State University; ANDERSON, JOE - Kansas State University; Bayles, Darrell; Falkenberg, Shollie

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/3/2018
Publication Date: 2/1/2019
Citation: Neill, J.D., Workman, A.M., Hesse, R., Bai, J., Poulsen-Porter, E., Meadors, B., Anderson, J., Bayles, D.O., Falkenberg, S.M. 2019. Identification of BVDV2b and 2c subgenotypes in the United States: genetic and antigenic characterization. Virology. 528:19-29. https://doi.org/10.1016/j.virol.2018.12.002.
DOI: https://doi.org/10.1016/j.virol.2018.12.002

Interpretive Summary: Bovine viral diarrhea virus (BVDV) is a common pathogen of cattle that causes mild to very severe disease in infected cattle. BVDV exists in two possible forms, cytopathic and noncytopathic, named for the effect they have on cultured epithelial cells. The noncytopathic form can establish a persistent infection in a calf if the infection occurs early in pregnancy before maturation of the fetal immune system. The resulting calf can be born normally and spread virus for the remainder of its life. Commercial vaccines containing strains of BVDV have been on the market for over 50 years. These vaccines still contain the same strains that were incorporated from the initial formulation. These vaccines have also been shown to have, at times, limited efficacy and do not provide levels of protection that are necessary to prevent 100% of fetal infections that result in the birth of persistently-infected calf. There has been no systematic study of the genetic and antigenic variation that exists in BVDV that are circulating in cattle herds. Thus, there is no true measure of how effective the current vaccines are in preventing infection by BVDV that are in cattle herds. In this study, BVDV isolates belonging to the BVDV2 species were examined to determine the amount of genetic and antigenic variation that exists. Comparison of the nucleotide sequences of as many as 103 of these viruses revealed that there was considerable genetic diversity and that the vaccine viruses in use were far removed from more genetically diverse strains examined. In addition, two new subgroups of BVDV2 were shown to be present in the U.S., complicating the protection afforded by the commercial vaccines. An antiserum against one BVDV strain used in vaccines was raised by infecting a calf. This antiserum was used in assays to determine its effectiveness in stopping infection by different BVDV isolates. This analysis revealed that as the amount of genetic differences increased in virus strains, the ability of the serum to prevent infection significantly decreased. This represents the first study examining in depth the amount of genetic diversity in BVDV, showing that as the amount of diversity increases, there is a corresponding decrease in the ability of an antisera to prevent infection.

Technical Abstract: Bovine viral diarrhea virus (BVDV), a ubiquitous pathogen of cattle, causes subclinical to severe acute disease. Two species of BVDV are recognized, BVDV1 and BVDV2 with BVDV1 divided into at least 21 subgenotypes and BVDV2 into 3 to 4 subgenotypes, most commonly using sequences from the 5’ untranslated region (5’ UTR). We report genomic sequencing of 8 BVDV2 isolates that did not segregate into the 2a subgenotype; but represented two additional BVDV2 subgenotypes. One new BVDV2 subgenotype was previously recognized only in Asia. The other seven viruses fell into a second subgenotype that was first reported in Brazil and the U.S. in 2002. Neutralization assays using antiserum raised against vaccine strain BVDV2a 296c revealed varying degrees of neutralization of genetically diverse BVDV2 isolates. Neutralization titers decreased from 1.4 to more than a four log(2) decrease. This study illustrated the considerable genetic and antigenic diversity in BVDV2 circulating in the U.S.