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 and, correspondingly, improved 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.

中文翻译：

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TMEM154 E35K 变体（单倍型 1 和 3）对绵羊慢病毒感染发生率和母羊终生暴露期间生产力的影响

绵羊进行性肺炎病毒 (OPPV) 是一种小型反刍动物慢病毒，在美国羊群中广泛传播。OPPV 感染是终生的，其影响是多系统的，对动物的福祉和生产力有重大影响。由绵羊跨膜蛋白 154 (TMEM154) 基因编码的第 35 位赖氨酸的蛋白质同种型（K35，单倍型“1”）与存在两个拷贝时的感染易感性降低相关（即双倍型“1,1”） . 相反，当存在至少一个拷贝时，在第 35 位具有谷氨酸的祖先蛋白质同种型（E35，单倍型“3”）与感染的高度易感性相关。TMEM154 K35 等位基因对母羊生产力的有益影响以前没有在受控挑战实验中测量过，并且是本研究的主要目标。具有 TMEM154 双倍型“1,1”的母羊；“1,3”；和“3,3”（n = 31、47 和 30，分别）由感染 OPPV 的水坝出生和饲养，并在持续自然暴露于 OPPV 的情况下进行管理。每隔 4 个月对母羊进行一次长达 5.5 年的血清学状态检测。双倍型“1,1”母羊的感染发生率为 6.5% 至 9.7%，显着低于双倍型“1,3”（60.5 至 97.3%）或“3,3”母羊（P < 0.001）。 64.0 至 91.4%）。此外，双倍型“1,1”母羊的发病率从 10 个月到 67 个月没有增加（P > 0.99），而双倍型“1,3”和“3,3”母羊的发病率稳步上升，直到在大约 52 个月时达到渐近线。从双倍型“1,1”的母羊暴露5.5年的每只母羊断奶的羔羊总数和重量远远超过（P≤0.05）双倍型“1, 3”和“3,3”，平均分别为 2.1 只羔羊和 40 公斤。本研究证实，TMEM154 双倍型“1,1”动物降低了 OPPV 感染的发生率，并相应地提高了生产力。在具有高频率 TMEM154 单倍型“3”的鸡群中，选择单倍型“1”似乎是减轻这种经济上重要疾病影响的经济有效的方法。