Department of Agricultural and Environmental Sciences, College of Agriculture, Tennessee State University, Nashville, TN, United States.
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, United States.
Front Immunol. 2019 Jun 25;10:1431. doi: 10.3389/fimmu.2019.01431. eCollection 2019.
Innate immune interferons (IFNs), particularly type I IFNs, are primary mediators regulating animal antiviral, antitumor, and cell-proliferative activity. These antiviral cytokines have evolved remarkable molecular and functional diversity to confront ever-evolving viral threats and physiological regulation. We have annotated IFN gene families across 110 animal genomes, and showed that IFN genes, after originating in jawed fishes, had several significant evolutionary surges in vertebrate species of amphibians, bats and ungulates, particularly pigs and cattle. For example, pigs have the largest but still expanding type I IFN family consisting of nearly 60 IFN-coding genes that encode seven IFN subtypes including multigene subtypes of IFN-α, -δ, and -ω. Whereas, subtypes such as IFN-α and -β have been widely studied in many species, the unconventional subtypes such as IFN-ω have barely been investigated. We have cross-species defined the IFN evolution, and shown that unconventional IFN subtypes particularly the IFN-ω subtype have evolved several novel features including: (1) being a signature multi-gene subtype expanding primarily in mammals such as bats and ungulates, (2) emerging isoforms that have superior antiviral potency than typical IFN-α, (3) highly cross-species antiviral (but little anti-proliferative) activity exerted in cells of humans and other mammalian species, and (4) demonstrating potential novel molecular and functional properties. This study focused on IFN-ω to investigate the immunogenetic evolution and functional diversity of unconventional IFN subtypes, which may further IFN-based novel antiviral design pertinent to their cross-species high antiviral and novel activities.
先天免疫干扰素（IFN），特别是 I 型 IFN，是调节动物抗病毒、抗肿瘤和细胞增殖活性的主要介质。这些抗病毒细胞因子在分子和功能上具有显著的多样性，以应对不断进化的病毒威胁和生理调节。我们已经在 110 种动物基因组中注释了 IFN 基因家族，并表明 IFN 基因起源于有颌鱼类后，在两栖动物、蝙蝠和有蹄类动物等脊椎动物物种中经历了几次显著的进化爆发，特别是猪和牛。例如，猪拥有最大但仍在扩展的 I 型 IFN 家族，包含近 60 个 IFN 编码基因，编码包括多基因亚型 IFN-α、-δ 和 -ω 的七种 IFN 亚型。然而，IFN-α 和 -β 等亚型在许多物种中得到了广泛研究，而 IFN-ω 等非常规亚型几乎没有得到研究。我们已经跨物种定义了 IFN 的进化，并表明非常规 IFN 亚型，特别是 IFN-ω 亚型，已经进化出了几个新的特征，包括：（1）是一个主要在蝙蝠和有蹄类哺乳动物中扩展的标志性多基因亚型；（2）出现了比典型 IFN-α 具有更高抗病毒效力的新同工型；（3）在人类和其他哺乳动物细胞中具有高度跨物种的抗病毒（但很少有抗增殖）活性；（4）表现出潜在的新的分子和功能特性。本研究集中研究 IFN-ω，以研究非常规 IFN 亚型的免疫遗传进化和功能多样性，这可能进一步推动基于 IFN 的新型抗病毒设计，使其与跨物种高抗病毒和新型活性相关。
