Vaccinia virus strains Lister, USSR and Evans express soluble and cell-surface tumour necrosis factor receptors
Vaccinia virus strains Lister, USSR and Evans express soluble and cell-surface tumour necrosis factor receptors
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DOI：
10.1099/0022-1317-80-4-949
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发表时间：
1999-04-01
影响因子：
3.8
通讯作者：
Smith, GL
中科院分区：
文献类型：
--
作者：
Alcamí, A;Khanna, A;Smith, GL
痘病毒编码一系列干扰宿主免疫功能的蛋白质，如黏液瘤和Shope纤维瘤病毒中最初描述的可溶型细胞因子受体、可溶型病毒肿瘤坏死因子受体(VTNFR)。牛痘病毒(CPV)编码3种vTNFR(CRMB、CRMC和CRMD)，与痘苗病毒(VV)哥本哈根株CRMB和CRMC等同的基因发生突变，分别命名为B28R/C22L和A53R。最近在CPV和ECtromelia病毒中发现了crmd基因，但在VV哥本哈根病毒中缺失了该基因。我们在18种正痘病毒感染的培养物中检测了人肿瘤坏死因子的可溶性结合活性的表达，发现大多数人的TNFR是由VV株Lister、USSR和Evans、CPV象痘和骆驼痘病毒产生的。有趣的是，我们还在VV Lister、USSR和Evans感染的细胞表面发现了TNFR活性，对VV Lister相关区域的序列分析证实了一个完整的A53R基因和一个失活的B28R基因。VV Lister A53R在杆状病毒和VV Western Reserve中的表达表明，A53R基因编码22 kDa的活性可溶性vTNFR，VV Lister(A53R)和CPV(CRMB和CRMC)的重组vTNFR具有相似的结合特异性，每个受体都能结合人、小鼠和大鼠的肿瘤坏死因子，但不结合人淋巴毒素-α。最后，VV Lister和CPV vTNFR以高亲和力结合人肿瘤坏死因子，并阻止肿瘤坏死因子与细胞受体的结合。
Poxviruses encode a broad range of proteins that interfere with host immune functions such as soluble versions of cytokine receptors, Soluble virus tumour necrosis factor receptors (vTNFRs) were described originally in myxoma and Shope fibroma viruses. Cowpox virus (CPV) encodes three vTNFRs (CrmB, CrmC and CrmD), The genes equivalent to CrmB and CrmC in vaccinia virus (VV) Copenhagen are mutated and are named B28R/C22L and A53R, respectively. CrmD was identified recently in CPV and ectromelia virus but the gene is absent in VV Copenhagen, We have tested for expression of soluble binding activity for human TNF in cultures infected with 18 orthopoxviruses and have found that TNFRs are mostly absent but are produced by VV strains Lister, USSR and Evans, by the CPV elephantpox and by camelpox virus. Interestingly, we also found TNFR activity on the surface of cells infected with VV Lister, USSR and Evans, Sequence analysis of the relevant regions in VV Lister identified an intact A53R gene and an inactive B28R gene. Expression of VV Lister A53R in baculovirus and VV Western Reserve demonstrated that gene A53R encodes an active soluble vTNFR of 22 kDa, Expression and characterization of recombinant vTNFRs from VV Lister (A53R) and CPV (CrmB and CrmC) showed a similar binding specificity, with each receptor binding TNF from man, mouse and rat, but not human lymphotoxin-alpha. Lastly, the VV Lister and CPV vTNFRs bind human TNF with high affinity and prevent the binding of TNF to cellular receptors.