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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 ovine TMEM154 associated with reduced risk of ovine lentivirus infection are also associated with reduced proviral concentration

Authors
item Alshanbari, Fahad -
item Mousel, Michelle
item Reynolds, James
item Hermann-Hoesing, Lynn -
item Heaton, Michael
item Lewis, Gregory
item Knowles, Donald
item White, Stephen

Submitted to: Annual International Plant & Animal Genome Conference
Publication Type: Abstract Only
Publication Acceptance Date: November 13, 2012
Publication Date: December 1, 2012
Citation: Alshanbari, F., Mousel, M.R., Reynolds, J.O., Hermann-Hoesing, L.M., Heaton, M.P., Lewis, G.S., Knowles Jr, D.P., White, S.N. 2012. Mutations in ovine TMEM154 associated with reduced risk of ovine lentivirus infection are also associated with reduced proviral concentration . Annual International Plant & Animal Genome Conference. Plant & Animal Genomes Conference XXI, Abstract 0624. San Diego, CA. January 14, 2013..

Interpretive Summary: Ovine lentivirus (OVLV), also known as ovine progressive pneumonia virus or maedi-visna, is very common in U.S. sheep (24% positive). This virus causes economic damage to the sheep industry through a range of disease symptoms, including pneumonia, arthritis, mastitis, body condition wasting, and encephalitis. There is no cure and no effective vaccine for preventing OVLV infection. However, breed differences in two measures of susceptibility to OVLV suggest it may be possible to breed healthier sheep. Mutations in the TMEM154 gene have been shown to confer reduced probability of a sheep becoming infected with OVLV under field conditions. However, there have been no studies of proviral concentration (a measure related to viral replication and pathological severity) in sheep with these TMEM154 mutations. We found that the favorable, low risk TMEM154 genotype is also associated with reduced OVLV proviral concentration in one flock. This extends previous findings by suggesting that breeding sheep with desirable TMEM154 genotypes may not only make the sheep less likely to get the virus, but also likely to get less severe disease even if they do get the virus. However, additional work to repeat these results in additional populations will be necessary to confirm widespread utility prior to using these mutations in making breeding decisions to reduce OVLV proviral concentration in domestic sheep.

Technical Abstract: Ovine lentivirus (OVLV), also called ovine progressive pneumonia virus or maedi-visna, is present in 24% of US sheep. Like human immunodeficiency virus, OVLV is macrophage-tropic lentivirus that causes lifelong infection. The adverse economic impact on the sheep industry is due to a range of disease symptoms, including pneumonia, arthritis, mastitis, body condition wasting, and encephalitis. Animals with high proviral concentration in peripheral blood show increased severity of pathological lesions, so proviral concentration can be a proxy for not only proviral replication but also disease severity. There is no cure and no effective vaccine for preventing OVLV infection. However, breed differences in prevalence and proviral concentration indicate a genetic basis for differential susceptibility to OVLV. Recently, it has been shown that sheep with two copies of TMEM154 encoding lysine (K) at position 35 (haplotype 1) are less susceptible to infection. In the current study, we genotyped TMEM154 and quantified proviral concentration in 340 ewes from a single Polypay flock with natural exposure. We found that two copies of TMEM154 haplotype 1 are also associated with reduced OVLV proviral concentration in sheep from this flock (P<0.02). This extends previous findings by suggesting that selection for sheep homozygous for TMEM154 haplotype 1 may reduce not only odds of OVLV infection, but also proviral replication and severity of pathological lesions among infected sheep. However, before TMEM154 is used as a selection tool to reduce OvLV proviral concentration, testing of additional sheep populations is necessary to confirm the association between TMEM154 diplotypes and proviral concentration.

Last Modified: 12/21/2014
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