|Clawson, Michael - Mike|
|Redden, Reid - North Dakota State University|
|Schuller, Genevieve - Gennie|
|Heaton, Michael - Mike|
|Chitko Mckown, Carol|
|Smith, Timothy - Tim|
Submitted to: Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/7/2015
Publication Date: 3/5/2015
Citation: Clawson, M.L., Redden, R., Schuller, G., Heaton, M.P., Workman, A.M., Chitko-McKown, C.G., Smith, T.P.L., Leymaster, K.A. 2015. Genetic subgroup of small ruminant lentiviruses that infects sheep homozygous for TMEM154 frameshift deletion mutation A4delta53. Veterinary Research. 46:22.
Interpretive Summary: Small Ruminant Lentiviruses (SRLVs) are viruses that infect domestic sheep and goats in the United States and throughout much of the world. The infections persist for the lifetime of the host, and result in a slow progression to disease and death. Common symptoms in sheep include pneumonia, mastitis, and a general wasting away syndrome known as cachexia. SRLV infections of sheep are influenced by genetics of both the host and the pathogen. On the host side, sheep vary in their susceptibility to SRLV infection due to variation within the ovine transmembrane 154 gene (TMEM154). On the pathogen side, specific SRLV subgroups, or “strains”, infect sheep in association with their TMEM154 variation. While the biological function of the TMEM154 protein is currently unknown, the association of SRLV strains with TMEM154 variants has indicated a possibility that the protein could be required for SRLV infection of sheep. However, in this study, we identified a new strain of SRLV in the United States that infected sheep that evidently did not make functional TMEM154 protein due to a mutation in the gene. Consequently, this strain doesn’t appear to require TMEM154 protein to infect sheep, and thus may not be hindered by TMEM154 variation in the infection process. It will be important to consider virus strain types when implementing sheep breeding programs that incorporate TMEM154 variation to control SRLV infection and disease.
Technical Abstract: Small Ruminant Lentivirus (SRLV) infections of sheep are influenced by genetics on both the host and pathogen sides. Genetic variation in the ovine transmembrane 154 (TMEM154) gene associates with infection susceptibility, and distinct SRLV genetic subtypes infect sheep in association with their TMEM154 diplotypes. In this study, a novel SRLV subtype was identified that naturally infected sheep with various TMEM154 diplotypes, including those homozygous for a rare frameshift mutation (A4delta53), which is predicted to abolish TMEM154 protein function. Thus, these SRLVs may infect sheep that lack functional TMEM154, and may not be restricted by TMEM154 diplotypes in establishing infections.