HOST IMMUNOGENETICS PREDICT CLINICAL DISEASES IN OVINE PROGRESSIVE PNEUMONIA VIRUS INFECTED SHEEP
Location: Animal Diseases Research
Title: Ovine progressive pneumonia provirus levels associate with breed and Ovar-DRB1
Submitted to: Immunogenetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 25, 2008
Publication Date: December 4, 2008
Citation: Hoesing, L.M., White, S.N., Mousel, M.R., Lewis, G.S., Knowles Jr, D.P. 2008. Ovine progressive pneumonia provirus levels associate with breed and Ovar-DRB1. Immunogenetics. 60(12):749-758.
Interpretive Summary: Previous research showed that specific breeds had lower ovine progressive pneumonia virus (OPPV) seroprevalence than other breeds. This suggested that there is a host genetic factor which could be affecting OPPV infection status. In this study, the host genetic marker, Ovar-DRB1, was evaluated for associations to OPP provirus loads in 383 sheep of the Rambouillet, Columbia, and Polypay breeds. Two Ovar-DRB1 expressed alleles (DRB1*0403 and DRB1*07012) and six Ovar-DRB1 genotypes encoding for Y31, T32, N37, T51, Q60 or N74 associated with lower OPP provirus load. In contrast, there were no Ovar-DRB1 expressed alleles that associated with the presence or absence of OPP provirus load, and there were no Ovar-DRB1 expressed alleles that associated with higher OPP provirus load. There were three Ovar-DRB1 genotypes encoding for H32, A38, or I67 that associated with higher OPP provirus load. Overall, these results suggest that Ovar-DRB1 contributes as an OPP provirus load controller especially in the Rambouillet breed. Prior to implementing breeding strategies, experimental infection studies need to be conducted to verify these associations and production trait analyses needs to be performed on the specific Ovar-DRB1 alleles and genotypes mentioned in this study.
Previous studies have suggested that host genetics influence both lung histopathology and seroprevalence in sheep infected with ovine progressive pneumonia virus (OPPV). As a first start, a genetic association study was conducted in 383 Idaho sheep of the Columbia, Polypay and Rambouillet breeds utilizing systemic OPP provirus load as a measure of infection and MHC class II Ovis aries (Ovar)-DRB1, a putative receptor for OPPV, as one candidate genetic marker. When evaluating breeds using only OPP provirus load, the Rambouillet breed were less likely to have an OPP provirus load as compared to Columbia sheep at ages 5 and 6 (P value <0.02), and they exhibited lower loads when compared to both Columbia and Polypay animals of the same ages (P value <0.05). To further investigate the genetic basis of these differences in control of viral infection, MHC class II Ovis aries (Ovar)-DRB1 expressed alleles and genotypes were identified and evaluated for an association with OPP provirus load. DRB1*0403 and DRB1*07012 expressed alleles significantly associated (P value=0.019, P value=0.0002, respectively) with lower OPP provirus load. In addition, encoded amino acids Y31, T32, N37, T51, Q60 or N74 in the DRB1 ß1 domain associated (P values ranged 0.0003-0.018) with lower OPP provirus load, whereas encoded amino acids H32, A38, or I67 associated (P value range=0.013-0.043) with higher OPP provirus load. The decrease in hydrophobicity and Van der Waals volume of the lower OPP provirus load-DRB1 genotypes (T32, N37, T51, Q60, N74) as opposed to the higher OPP provirus load-DRB1 genotypes (H32, A38, I67) may allow for expansion of the peptide-binding site in the ß1 domain to bind more OPPV peptides and produce a more effective immune response.