Changes introduced in the open reading frame of bovine viral diarrhea virus during serial infection of pregnant swine

Authors: KUCA, THIBAUD - Auburn University; PASSLER, THOMAS - Auburn University; NEWCOMER, BENJAMIN - Auburn University; Neill, John; GALIK, PATRICIA - Auburn University; RIDDELL, KAY - Auburn University; ZHANG, YIJING - Auburn University; WALZ, PAUL - Auburn University

Submitted to: Frontiers in Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/5/2020
Publication Date: 6/10/2020
Citation: Kuca, T., Passler, T., Newcomer, B.W., Neill, J.D., Galik, P.K., Riddell, K.P., Zhang, Y., Bayles, D.O., Walz, P.H. 2020. Changes introduced in the open reading frame of bovine viral diarrhea virus during serial infection of pregnant swine. Frontiers in Microbiology. 11:1138. https://doi.org/10.3389/fmicb.2020.01138.
DOI: https://doi.org/10.3389/fmicb.2020.01138

Interpretive Summary: Bovine viral diarrhea virus (BVDV) is a ubiquitous pathogen of cattle, causing disease that ranges from subclinical to severe acute hemorrhagic syndrome. BVDV is most commonly isolated from cattle but can also cause disease in and be isolated from sheep, goats, deer, camelids and pigs. BVDV exist in two forms, cytopathic and noncytopathic. When a susceptible animal is infected with a noncytopathic BVDV strain in the first trimester of pregnancy, the fetus can become persistently-infected, and following birth,spread the virus for the remainder of its life. The BVDV RNA genome encodes a single large protein. This protein is processed to produce the final viral proteins. BVDV is also known for rapid rate of genetic change. More changes are introduced into the genomic RNA during infections of pregnant animals. The enzyme responsible for copying the RNA genomes of these viruses is known to introduce errors at a relatively high rate during the infection process. Many of the changes are found in the virus envelope proteins that can resist previous immunity. Changes have also been noted that appear to make it possible for BVDV to more efficiently infect species other than cattle. This study was conducted to examine the changes that occur in the genomic RNA of BVDV that caused sequential infections in pregnant swine, a surprising non-ruminant host. The goal was to define changes that occurred in BVDV that may be involved in changing immune characteristics as well as changes that may enhance infection of pigs. Sequence analysis of the viruses isolated from infected piglets revealed that changes occurred in the first pregnant pig infected and that these changes were maintained through following infection cycles. This was most likely due to changes that had to occur in adaptation to the new host. After several sequential infections, the number of changes was reduced, probably because no further changes enhanced infection of pigs. This experiment provided insight into how BVDV adapts to a new host and may indicate the pig as a source of genetic change.

Technical Abstract: Bovine viral diarrhea virus (BVDV) is an economically important pathogen of cattle, but this virus can also infect pigs, camelids, and a wide range of domestic and wild ruminants. BVDV isolates circulating in animal populations are genetically and antigenically highly diverse. Previous studies demonstrated that many substitutions were introduced in the viral genome during acute BVDV infections in cattle. Furthermore, greater numbers of substitutions occurred in pregnant sheep than in pregnant cattle during serial infection with a BVDV isolate of bovine origin. To our knowledge, genomic changes arising during BVDV infections in swine have not been investigated. The purpose of this study was to determine the changes introduced in the open reading frame (ORF) of the BVDV genome during serial infection of pregnant swine with an isolate of bovine origin. Serial inoculations were performed in six pregnant gilts using the BVDV-1b isolate AU526 in the first gilt and serum from the preceding acutely infected gilt thereafter. The complete ORF sequences of 14 BVDV-1b isolates obtained from acutely infected gilts and their congenitally infected piglets were determined. Sequence comparison revealed that many nucleotide and amino acid substitutions occurred during serial infection of pregnant swine. Furthermore, 12 identical amino acid substitutions were detected in all porcine isolates, four of which occurred in the E2 coding region. These results suggest that BVDV infections in pregnant swine may serve as a significant source of viral genetic variability and may be associated with adaptive changes.