Identification of amino acid changes in the envelope glycoproteins of bovine viral diarrhea viruses isolated from alpaca that may be involved in host adaptation

Authors: Neill, John; DUBOVI, EDUARD - Cornell University; Ridpath, Julia

Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/5/2015
Publication Date: 6/11/2015
Publication URL: http://handle.nal.usda.gov/10113/61357
Citation: Neill, J.D., Dubovi, E.J., Ridpath, J.F. 2015. Identification of amino acid changes in the envelope glycoproteins of bovine viral diarrhea viruses isolated from alpaca that may be involved in host adaptation. Veterinary Microbiology. http://dx.doi.org/10.1016/j.vetmic.2015.06.007.

Interpretive Summary: Bovine viral diarrhea viruses (BVDV) are most commonly associated with infections in cattle. However, it has been shown that BVDV causes disease in most ruminants. Recently, multiple BVDV isolations have been made from both transiently and persistently infected alpaca. Here, we show that, with the exception of one virus isolate from alpaca, all were multiple isolations of the same virus strain that was passing through domestic alpaca herds. Following determination of the nucleotide sequences that encode viral proteins, three areas encoded amino acid changes that were unique to the alpaca isolates. Changes that were observed were small deletions, amino acid changes that affected the E2 envelope glycoprotein and changes that affected the Erns envelope glycoprotein. The single isolate not related to the single strain viruses also possessed these changes. These alterations found in these viruses appeared to have increased infection by optimizing the infection process of the alpaca host. This is the first report describing changes that may alter the host tropism of BVDV.

Technical Abstract: Bovine viral diarrhea viruses (BVDV) are most commonly associated with infections of cattle. However, BVDV is often isolated from closely related ruminants with a number of BVDV-1b viruses being isolated from alpacas that were both acutely and persistently infected (PI). The complete nucleotide sequence of the open reading frame (ORF) of eleven alpaca BVDV isolates and the region encoding the envelope glycoproteins of an additional three isolates were determined. With the exception of one, all alpaca isolates were > 99.2% similar at the nucleotide level. The Hercules isolate was more divergent, with 95.7% sequence identity to the other viruses. Comparison of amino acid sequences of alpaca and bovine-derived BVDV strains revealed three regions with amino acid sequences unique to alpaca isolates. The first contained two small in-frame deletions near the N-terminus of the E2 glycoprotein. The second was found near the C-terminus of the E2 protein. Here, four altered amino acids were located within a 30 amino acid domain that participates in E2 homodimerization. The third region contained three variable amino acids in the C-terminus of the Erns within the amphipathic helix membrane anchor. These changes were found in the polar side of the amphipathic helix and may have resulted in an increased charge within the polar face. High sequence similarity of the 14 viruses indicated that they were isolates of a single BVDV strain that had adapted to and were circulating through alpaca herds. Hercules was a more distantly related strain that has been isolated only once in Canada and represented a separate adaptation event that possessed the same adaptive changes.