Zoonotic orthopoxviruses encode a high-affinity antagonist of NKG2D
Zoonotic orthopoxviruses encode a high-affinity antagonist of NKG2D
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DOI：
10.1084/jem.20062026
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发表时间：
2007-06-11
影响因子：
15.3
通讯作者：
Carayannopoulos, Leonidas N.
中科院分区：
文献类型：
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作者：
Campbell, Jessica A.;Trossman, David S.;Carayannopoulos, Leonidas N.
NK和T淋巴细胞表达主要组织相容性复合体I类超家族（MHCISF）的各种成员的激活和抑制受体。为了逃避免疫细胞毒性，许多病毒干扰这些受体的功能，通常是通过改变宿主细胞上MHCISF蛋白的显示谱。利用结构受限的隐马尔可夫模型，我们发现了一种正痘病毒蛋白，其本身与I类类似，可作为NKG2D激活受体的竞争性拮抗剂。这种正痘病毒MHC i类蛋白（OMCP）在牛痘和猴痘病毒中保守，由感染细胞分泌，与啮齿动物和人的NKG2D具有高亲和力结合（K-D分别接近30 nM和0.2 nM）。OMCP阻断宿主编码配体的识别，抑制NK细胞依赖nkg2d的杀伤。这一发现代表了病毒干扰NKG2D的新机制，并揭示了针对新出现的正痘病毒的先天免疫的细胞间识别事件。
NK and T lymphocytes express both activating and inhibiting receptors for various members of the major histocompatibility complex class I superfamily (MHCISF). To evade immunologic cytotoxicity, many viruses interfere with the function of these receptors, generally by altering the displayed profile of MHCISF proteins on host cells. Using a structurally constrained hidden Markov model, we discovered an orthopoxvirus protein, itself distantly class I - like, that acts as a competitive antagonist of the NKG2D activating receptor. This orthopoxvirus MHC class I-like protein (OMCP) is conserved among cowpox and monkeypox viruses, secreted by infected cells, and bound with high affinity by NKG2D of rodents and humans (K-D similar to 30 and 0.2 nM, respectively). OMCP blocks recognition of host-encoded ligands and inhibits NKG2D-dependent killing by NK cells. This finding represents a novel mechanism for viral interference with NKG2D and sheds light on intercellular recognition events underlying innate immunity against emerging orthopoxviruses.