|Heaton, Michael - Mike|
|Chitko Mckown, Carol|
|Smith, Timothy - Tim|
|Clawson, Michael - Mike|
Submitted to: Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/12/2013
Publication Date: 7/29/2013
Citation: Sider, L.H., Heaton, M.P., Chitko-Mckown, C.G., Harhay, G.P., Smith, T.P.L., Leymaster, K.A., Laegreid, W.W., and Clawson, M.L. 2013. Small ruminant lentivirus genetic subgroups associate with sheep TMEM154 genotypes. Veterinary Research. 44:64. DOI: 10.1186/1297-9716-44-64. Interpretive Summary: Small Ruminant Lentiviruses (SRLVs) are viruses that infect domestic sheep throughout much of the world. SRLV infections persist for life, and can cause progressive, debilitating inflammatory diseases such as pneumonia and mastitis, and eventual death. Sheep have varying levels of susceptibility to SRLV infection due to variation within the ovine transmembrane 154 gene (TMEM154). As a result, some sheep are at greater risk of infection than others. However, SRLVs evolve at accelerated rates and thus are genetically diverse and highly adaptable. In this study, we wanted to know if SRLVs have evolved, or are evolving to infect sheep with different TMEM154 variants. We identified two major genetic subtypes of SRLVs infecting sheep in the United States, and found that they were each associated with specific TMEM154 variants. These results indicate that SRLV strains vary by their ability to infect sheep with different TMEM154 variants. Consequently, it may be important to consider virus strain types when implementing sheep breeding programs that incorporate TMEM154 variation.
Technical Abstract: Small ruminant lentiviruses (SRLVs) are prevalent in North American sheep and a major cause of production losses for the U.S. sheep industry. Sheep susceptibility to SRLV infection is influenced by genetic variation within the ovine transmembrane 154 gene (TMEM154). Animals with either of two distinct TMEM154 haplotypes that both encode glutamate at position 35 of the protein (E35) are at greater risk of SRLV infection than those homozygous with a K35 haplotype. Prior to this study, it was unknown if TMEM154 associations with infection are influenced by SRLV genetic subgroups. Accordingly, our goals were to characterize SRLV subgroups naturally infecting sheep from a diverse U.S. Midwestern flock and test them for associations with TMEM154 E35K genotypes. Two regions of the SRLV genome were targeted for proviral amplification, cloning, sequence analysis, and association testing with TMEM154 E35K genotypes: gag and the transmembrane region of env. Independent analyses of gag and env sequences showed that they clustered in two subgroups (1 and 2), they were distinct from SRLV subtypes originating from Europe, and that subgroup 1 associated with hemizygous and homozygous TMEM154 K35 genotypes and subgroup 2 with hemi-, heterozygous, and homozygous E35 genotypes (gag p<0.001, env p=0.049). These results indicate that Subgroup 1 SRLVs are more likely to overcome the host genetic barrier to infection associated with TMEM154 K35 (gag RR=2.66, env RR=1.92). Consequently, both host and SRLV genotypes affect the relative risk of SRLV infection in sheep.