Mutations in Ovine TMEM154 Associated with Reduced Risk of Ovine Lentivirus Infection are also Associated with Reduced Proviral Concentration

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.