College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, Guangzhou 510642, China.
Viruses. 2023 Jan 30;15(2):393. doi: 10.3390/v15020393.
Canine influenza virus (CIV) significantly threatens the canine population and public health. Tetherin, an innate immune factor, plays an important role in the defense against pathogen invasion and has been discovered to restrict the release of various enveloped viruses. Two isoforms of canine tetherin (tetherin-X1 and tetherin-X2) were identified in peripheral blood leukocytes of mixed-breed dogs using reverse transcription polymerase chain reaction (RT-PCR). Amino acid alignment revealed that relative to full-length tetherin (tetherin-X1) and truncated canine tetherin (tetherin-X2) exhibited deletion of 34 amino acids. The deletion occurred at the C-terminus of the coiled-coiled ectodomain and the N-terminus of the glycosylphosphatidylinositol (GPI)-anchor domain. Tetherin-X2 was localized subcellularly at the cell membrane, which was consistent with the localization of tetherin-X1. In addition, canine tetherin-X1 and tetherin-X2 restricted the release of H3N2 CIV. However, canine tetherin-X1 had higher antiviral activity than canine tetherin-X2, indicating that the C-terminus of the coiled-coiled ectodomain and the N-terminus of the GPI-anchor domain of canine tetherin (containing the amino acids deleted in tetherin-X2) are critical for its ability to restrict H3N2 CIV release. This study provides insights for understanding the key functional domains of tetherin that restrict CIV release.
犬流感病毒（CIV）对犬群和公共卫生构成了重大威胁。 tetherin 是一种先天免疫因子，在抵御病原体入侵方面发挥着重要作用，并且已被发现可以限制各种包膜病毒的释放。通过逆转录聚合酶链反应（RT-PCR），在杂种犬的外周血白细胞中鉴定出两种犬 tetherin（tetherin-X1 和 tetherin-X2）同工型。氨基酸序列比对表明，与全长 tetherin（tetherin-X1）和截短的犬 tetherin（tetherin-X2）相比，tetherin-X2 缺失了 34 个氨基酸。缺失发生在卷曲螺旋胞外域的 C 末端和糖基磷脂酰肌醇（GPI）锚定域的 N 末端。Tetherin-X2 亚细胞定位在细胞膜上，与 tetherin-X1 的定位一致。此外，犬 tetherin-X1 和 tetherin-X2 限制了 H3N2 CIV 的释放。然而，犬 tetherin-X1 比犬 tetherin-X2 具有更高的抗病毒活性，表明犬 tetherin（包含 tetherin-X2 缺失的氨基酸）的卷曲螺旋胞外域的 C 末端和 GPI 锚定域的 N 末端对于其限制 H3N2 CIV 释放的能力至关重要。本研究为理解限制 CIV 释放的 tetherin 的关键功能域提供了新的认识。
