School of Public Health, Weifang Medical University, Weifang 261042, Shandong, China.
School of Public Health, Weifang Medical University, Weifang 261042, Shandong, China.
Poult Sci. 2023 Jul;102(7):102724. doi: 10.1016/j.psj.2023.102724. Epub 2023 Apr 16.
The placenta-specific 8 (PLAC8) gene, also known as ONZIN or C15, codes for a cysteine-rich peptide originally identified in mouse placental tissue and subsequently identified in a variety of epithelial tissues and immune cells. PLAC8 is also expressed in birds, such as ducks, where its functional roles remain unknown. Here, we aimed to determine the mRNA and protein expression profiles and the functional role of duck PLAC8 during the infection of duck hepatitis A virus type 1 (DHAV-1). We found that the duck PLAC8 is also a cysteine-rich polypeptide composed of 114 amino acid residues, with no signal peptide. Duck PLAC8 is highly expressed in the immune organs of young cherry valley ducks, including the thymus, bursa fabricius, and spleen. However, it has negligible expression level in liver, brain, kidney, and heart. Additionally, PLAC8 expression was considerably induced after DHAV-1 infection both in vitro and in vivo, especially in the immune organs of ducklings. This tissue expression distribution and induction upon infection suggest that PLAC8 might play a critical role in innate immunity. Our data showed that PLAC8 significantly suppressed the expression of Toll-like receptor 7 (TLR7), leading to decreased expression of downstream signaling molecules including myeloid differentiation primary response gene 88 (MyD88) and nuclear factor kappa-B (NF-κB). This ultimately resulted in low levels of type I interferon and interleukin 6 (IL-6). Additionally, PLAC8 positively regulated DHAV-1 replication levels. RNAi against PLAC8 in duck embryo fibroblasts considerably inhibited DHAV-1 propagation, while PLAC8 overexpression significantly facilitated DHAV-1 replication.
胎盘特异性 8 （PLAC8）基因，也称为 ONZIN 或 C15，编码一种最初在鼠胎盘组织中发现的富含半胱氨酸的肽，随后在各种上皮组织和免疫细胞中被发现。PLAC8 也在鸟类中表达，例如鸭子，其功能作用尚不清楚。在这里，我们旨在确定鸭 PLAC8 在感染鸭甲型肝炎病毒 1 （DHAV-1）期间的 mRNA 和蛋白表达谱及其功能作用。我们发现，鸭 PLAC8 也是一种富含半胱氨酸的多肽，由 114 个氨基酸残基组成，没有信号肽。鸭 PLAC8 在樱桃谷雏鸭的免疫器官中高度表达，包括胸腺、法氏囊和脾脏。然而，它在肝脏、大脑、肾脏和心脏中的表达水平极低。此外，PLAC8 在体外和体内感染 DHAV-1 后表达水平显著升高，尤其是在雏鸭的免疫器官中。这种组织表达分布和感染诱导表明 PLAC8 可能在固有免疫中发挥关键作用。我们的数据表明，PLAC8 显著抑制了 Toll 样受体 7（TLR7）的表达，导致下游信号分子包括髓样分化初级反应基因 88（MyD88）和核因子 kappa-B（NF-κB）的表达降低。这最终导致 I 型干扰素和白细胞介素 6（IL-6）水平降低。此外，PLAC8 正向调节 DHAV-1 的复制水平。在鸭胚成纤维细胞中针对 PLAC8 的 RNAi 极大地抑制了 DHAV-1 的增殖，而 PLAC8 的过表达显著促进了 DHAV-1 的复制。
