Kojima-Shibata Chihiro, Shinkai Hiroki, Morozumi Takeya, Jozaki Kosuke, Toki Daisuke, Matsumoto Toshimi, Kadowaki Hiroshi, Suzuki Eisaku, Uenishi Hirohide
Miyagi Livestock Experimental Station, Miyagi Prefecture, 1 Hiwatashi, Minamisawa, Iwadeyama, Osaki, Miyagi, Japan.
Immunogenetics. 2009 Feb;61(2):153-60. doi: 10.1007/s00251-008-0350-y. Epub 2008 Dec 20.
Pathogens localized extracellularly or incorporated into endosomes are recognized mainly by Toll-like receptors, whereas pathogens and pathogen-derived molecules that invade into the cytoplasm of host cells typically are recognized by intracellular pattern recognition receptors (PRRs), such as retinoic acid-inducible gene (RIG)-like helicases (RLHs) and nucleotide-binding oligmerization domain (NOD)-like receptors (NLRs). RIG-I and melanoma differentiation-associated gene 5 (MDA5), which belong to the RLH family, recognize viral genomic RNA, whereas NOD2, a member of the NLR family, responds to microbial peptidoglycans. These receptors may play an important role in pig opportunistic infectious diseases, such as pneumonia and diarrhea, which markedly impair livestock productivity, such that polymorphisms of these receptor genes are potential targets of pig breeding to increase disease resistance. Here, we report single nucleotide polymorphisms (SNPs) in porcine DDX58, IFIH1, and NOD2, which encode RIG-I, MDA5, and NOD2, respectively. Interestingly, compared with DDX58 and IFIH1, NOD2 abounded in nonsynonymous SNPs both throughout the coding sequence and in sequences encoding domains important for ligand recognition, such as helicase domains for RIG-I and MDA5 and leucine-rich repeats in NOD2. These differences in the distribution of SNPs in intracellular PRRs may parallel the diversity of their ligands, which include nucleic acids and peptidoglycans.
定位于细胞外或整合到内体中的病原体主要由Toll样受体识别,而侵入宿主细胞质的病原体和病原体衍生分子通常由细胞内模式识别受体(PRR)识别,如视黄酸诱导基因(RIG)样解旋酶(RLH)和核苷酸结合寡聚化结构域(NOD)样受体(NLR)。属于RLH家族的RIG-I和黑色素瘤分化相关基因5(MDA5)识别病毒基因组RNA,而NLR家族成员NOD2对微生物肽聚糖有反应。这些受体可能在猪的机会性传染病如肺炎和腹泻中起重要作用,这些疾病会显著损害家畜生产力,因此这些受体基因的多态性是猪育种中提高抗病性的潜在靶点。在此,我们报告了猪DDX58、IFI1H和NOD2中的单核苷酸多态性(SNP),它们分别编码RIG-I、MDA5和NOD2。有趣的是,与DDX58和IFI1H相比,NOD2在整个编码序列以及编码对配体识别重要的结构域的序列中存在大量非同义SNP,如RIG-I和MDA5的解旋酶结构域以及NOD2中的富含亮氨酸重复序列。细胞内PRR中SNP分布的这些差异可能与其配体的多样性平行,其配体包括核酸和肽聚糖。