Effect of TMEM154 E35K variant (haplotypes 1 and 3) on the incidence of ovine lentivirus infection and ewe productivity during lifetime exposure

Authors: Murphy, Thomas - Tom; Chitko-Mckown, Carol; Heaton, Michael - Mike; Freking, Bradley - Brad

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/18/2021
Publication Date: 10/21/2021
Citation: Murphy, T.W., Chitko-McKown, C.G., Heaton, M.P., Freking, B.A. 2021. Effect of TMEM154 E35K variant (haplotypes 1 and 3) on the incidence of ovine lentivirus infection and ewe productivity during lifetime exposure. Journal of Animal Science. 99(11). Article skab304. https://doi.org/10.1093/jas/skab304.
DOI: https://doi.org/10.1093/jas/skab304

Interpretive Summary: Ovine progressive pneumonia (OPP) is multi-systemic disease caused by infection of a virus. The disease has major animal welfare and productivity implications as clinical signs of infection include labored breathing, hard udder, arthritis, and wasting. Moreover, OPP is incurable and no effective vaccines have been developed. It was most recently estimated that 36% of U.S. flocks have at least one OPP infected animal. Scientists at the U.S. Meat Animal Research Center first reported that variants within the ovine transmembrane protein 154 (TMEM154) gene are associated with susceptibility to OPP. Past studies revealed that animals with two copies of haplotype 1 (i.e., diplotype "1,1") are less susceptible to OPP than animals with one or more copies of halotpye 3 (i.e., diplotype "1,3" or "3,3"). However, differences in OPP susceptibility among TMEM154 diplotypes over a ewe's productive life have not been previously reported. Furthermore, potential associated effects of TMEM154 diplotypes on ewe productivity are not known. This study evaluated infection status and reproductive performance of TMEM154 diplotype "1,1"; "1,3"; and "3,3" ewes (n = 31, 47, and 30, respectively) over 5.5 years. All ewes were naturally and continually exposed to the OPP virus from birth until they left the flock. The incidence of OPP viral infection in ewes with diploptye “1,1” was 6.5 to 9.7% which was much lower than ewes with diplotype “1,3” or "3,3" (60.5 to 97.3%). Furthermore, the incidence of infection among ewes with diplotype “1,1” did not increase after 10 months of age, whereas infection rate among diplotype “1,3” and “3,3” ewes increased steadily until 52 months of age. Diplotype “1,1” ewes weaned, on average, 2.1 more lambs and 40 kg greater weight of lamb through 5 production years than diplotype “1,3” or “3,3” ewes. Based on an average price of lambs marketed during the years of this study, this equates to $171 in additional lifetime revenue per TMEM154 diplotype “1,1” ewe. Reduced productivity of diplotype “1,3” and “3,3” ewes is expected to be due to associated effects of clinical and subclinical OPP rather than direct effects of TMEM154 diplotype. Increasing the frequency of TMEM154 diplotype “1,1” within flocks facing challenges from OPP is an effective strategy to mitigate the effects of this costly disease.

Technical Abstract: Ovine progressive pneumonia virus (OPPV) is a small ruminant lentivirus that is widespread throughout U.S. sheep flocks. Infections with OPPV are lifelong and effects are multi-systemic with significant implications for animal well-being and productivity. A protein isoform with lysine at position 35 (K35, haplotype “1”) encoded by the ovine transmembrane protein 154 (TMEM154) gene has been associated with reduced susceptibility to infection when two copies are present (i.e., diplotype “1,1”). Conversely, the ancestral protein isoform with glutamate at position 35 (E35, haplotype “3”) is associated with high susceptibility to infection when at least one copy is present. The beneficial effect of TMEM154 K35 alleles on ewe productivity has not been previously measured in controlled challenge experiments and was a major objective of this study. Ewes with TMEM154 diplotypes “1,1”; “1,3”; and “3,3” (n = 31, 47, and 30, respectively) were born and reared by OPPV-infected dams and managed under continual natural exposure to OPPV. Ewes were tested for serological status at 4 mo intervals for up to 5.5 yr. The incidence of infection in ewes with diplotype “1,1” was 6.5 to 9.7% and significantly lower (P < 0.001) than ewes with diplotype “1,3” (60.5 to 97.3%) or “3,3” (64.0 to 91.4%). Furthermore, the incidence among ewes with diplotype “1,1” did not increase from 10 to 67 mo of age (P > 0.99), whereas the incidence among diplotype “1,3” and “3,3” ewes increased steadily until reaching an asymptote at approximately 52 mo of age. Total number and weight of lamb weaned per ewe exposed through 5.5 yr from ewes with diplotype “1,1” far exceeded (P <= 0.05) those with diplotypes “1,3” and “3,3” by, on average, 2.1 lambs and 40 kg, respectively. The present study confirmed that TMEM154 diplotype “1,1” animals have reduced incidence of OPPV infection throughout their productive life and, correspondingly, improved lifetime productivity. In flocks with a high frequency of TMEM154 haplotype “3”, selection for haplotype “1” appears to be a cost-effective approach to mitigate the impact of this economically important disease.