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United States Department of Agriculture

Agricultural Research Service

Research Project: Control of Ovine Respiratory Disease through Genetic and Immunologic Mitigation of Pathogen Transmission and Disease

Location: Animal Diseases Research

Title: Mutations in Ovis aries TMEM154 are associated with lower small ruminant lentivirus proviral concentration in one sheep flock

Authors
item Alshanbari, Fahad -
item Mousel, Michelle
item Reynolds, James
item Herrmann-Hoesing, Lynn -
item Highland, Margaret
item Lewis, Gregory
item White, Stephen

Submitted to: Animal Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 5, 2014
Publication Date: August 1, 2014
Citation: Alshanbari, F.A., Mousel, M.R., Reynolds, J.O., Herrmann-Hoesing, L.M., Highland, M.A., Lewis, G.S., White, S.N. 2014. Mutations in Ovis aries TMEM154 are associated with lower small ruminant lentivirus proviral concentration in one sheep flock. Animal Genetics. 45(4):565-571.

Interpretive Summary: Small ruminant lentivirus (SRLV), also called ovine progressive pneumonia virus or maedi-visna, is present in 24% of U.S. sheep. SRLV causes a range of disease symptoms, including pneumonia, mastitis, and body condition wasting. There is no cure and no effective vaccine for preventing SRLV infection, but there is a genetic basis for susceptibility to SRLV so selective breeding to reduce susceptibility may be possible. In the present study, we examined the relationship between SRLV control post-infection and variants in two genes, TMEM154 and CCR5, in 4 flocks containing 2,236 sheep. We found two copies of TMEM154 haplotype 1 (enocding lysine at amino acid position 35) were associated with reduced SRLV proviral concentration in one flock (P<0.02). This identified the same favorable genotype for SRLV control post-infection as previous work did for odds of SRLV infection, so it might be possible to use variants of the TMEM154 gene to improve both simultaneously. However, the frequencies of undesirable TMEM154 gene variants were too low in the other 3 flocks to test, so additional validation is necessary. The CCR5 promoter deletion did not have consistent association with SRLV proviral concentration, so it is not recommended for marker-assisted selection to improve control of SRLV post-infection. Future validation work in flocks with more balanced allele frequencies is needed to confirm or refute the TMEM154 association with control of SRLV post-infection in one sheep flock.

Technical Abstract: Small ruminant lentivirus (SRLV), also called ovine progressive pneumonia virus or maedi-visna, is present in 24% of U.S. sheep. Like human immunodeficiency virus, SRLV is a macrophage-tropic lentivirus that causes lifelong infection. The production impacts from SRLV are due to a range of disease symptoms, including pneumonia, arthritis, mastitis, body condition wasting, and encephalitis. There is no cure and no effective vaccine for preventing SRLV infection. However, breed differences in prevalence and proviral concentration indicate a genetic basis for susceptibility to SRLV. Animals with high blood proviral concentration show increased tissue lesion severity, so proviral concentration represents a live animal test for control post-infection in terms of proviral replication and disease severity. Recently, it was found that sheep with two copies of TMEM154 haplotype 1 (encoding lysine at position 35) had lower odds of SRLV infection. In the present study, we examined the relationship between SRLV control post-infection and variants in two genes, TMEM154 and CCR5, in 4 flocks containing 2236 sheep. We found two copies of TMEM154 haplotype 1 were associated with reduced SRLV proviral concentration in one flock (P<0.02), which identified the same favorable diplotype for control post-infection as for odds of infection. However, the frequencies of undesirable TMEM154 alleles were too low in the other 3 flocks to test. The CCR5 promoter deletion did not have consistent association with SRLV proviral concentration. Future work in flocks with more balanced allele frequencies is needed to confirm or refute TMEM154 association with control of SRLV post-infection.

Last Modified: 11/23/2014
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