Association of TMEM154 missense mutations with lentiviral infection and virus subtypes in sheep

Abstract Text: Small ruminant lentivirus (SRLV) infections are a major cause of production losses in many sheep industries.  Genetic susceptibility to SRLV infection in sheep is associated with the transmembrane protein 154 gene (TMEM154).  A lysine mutation affecting the extracellular domain (K35, variant 1) is associated with significant reduction in infection rate.  In production environments, the incidence of SRLV in ewes homozygous with variant 1 can be one eighth that of ewes with the variants encoding glutamate (E35, variants 2 or 3).  The highly-susceptible, ancestral variant 3 allele shows complete dominance compared to variant 1.  Twelve variants encoding different amino acid sequences have been identified in sheep, including frameshift deletions predicted to obliterate TMEM154 function.  Distinct SRLV genetic subgroups are associated with E35 and K35 variants, suggesting a direct interaction. Managing genetic variation in the TMEM154gene may help reduce, and then eradicate, SRLV in affected flocks.

Keywords: Sheep, SRLV, TMEM154