Epstein-Barr virus BARF1 protein is dispensable for B-cell transformation and inhibits alpha interferon secretion from mononuclear cells
Epstein-Barr virus BARF1 protein is dispensable for B-cell transformation and inhibits alpha interferon secretion from mononuclear cells
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DOI：
10.1128/jvi.73.9.7627-7632.1999
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发表时间：
1999-09-01
影响因子：
5.4
通讯作者：
Lekstrom, K
中科院分区：
文献类型：
--
作者：
Cohen, JI;Lekstrom, K
eb病毒（EBV） BARF1基因编码可溶性集落刺激因子1 （CSF-1）受体，该受体在体外中和CSF-1的作用。为了研究BARF1对EBV诱导的转化的影响，我们在EBV存在的情况下将重组BARF1加入B细胞。BARF1对eb病毒对B细胞的转化没有促进作用。为了研究BARF1在EBV感染中的作用，我们构建了一个BARF1基因大缺失后带有停止密码子的重组EBV突变体和一个带有野生型BARF1基因的重组病毒。虽然BARF1先前已被证明在几种细胞系中作为致癌基因，但EBV BARF1缺失突变体转化B细胞并引发潜伏感染，并且用BARF1突变体病毒转化的B细胞诱导SCID小鼠的肿瘤，其效率与野生型重组病毒相似。由于人CSF-1刺激单核细胞分泌α -干扰素，而BARF1编码可溶性CSF-1受体，我们研究了重组BARF1或来源于ebv感染的B细胞的BARF1是否能抑制α -干扰素的分泌。重组BARF1以剂量依赖的方式抑制单个核细胞分泌α干扰素。与野生型重组病毒转化的B细胞相比，突变型BARF1 EBV转化的B细胞对人单核细胞分泌α干扰素的抑制作用降低。这些实验表明，从EBV基因组中表达的BARF1直接抑制α干扰素的分泌，这可能调节了先天宿主对病毒的反应。
The Epstein-Barr virus (EBV) BARF1 gene encodes a soluble colony-stimulating factor 1 (CSF-1) receptor that neutralizes the effects of CSF-1 in vitro. To study the effect of BARF1 on EBV-induced transformation, we added recombinant BARF1 to B cells in the presence of EBV. BARF1 did not enhance transformation of B cells by EBV in vitro. To study the role of BARF1 in the context of EBV infection, we constructed a recombinant EBV mutant with a large deletion followed by stop codons in the BARF1 gene as well as a recombinant virus with a wild-type BARF1 gene. While BARF1 has previously been shown to act as an oncogene in several cell lines, the EBV BARF1 deletion mutant transformed B cells and initiated latent infection, and the B cells transformed with the BARF1 mutant virus induced tumors in SCID mice with an efficiency similar to that of the wild-type recombinant virus. Since human CSF-1 stimulates secretion of alpha interferon from mononuclear cells and BARF1 encodes a soluble CSF-1 receptor, we examined whether recombinant BARF1 or BARF1 derived from EBV-infected B cells could inhibit alpha interferon secretion. Recombinant BARF1 inhibited alpha interferon secretion by mononuclear cells in a dose-dependent fashion. The B cells transformed with mutant BARF1 EBV showed reduced inhibition of alpha interferon secretion by human mononuclear cells when compared with the B cells transformed with wild-type recombinant virus. These experiments indicate that BARF1 expressed from the EBV genome directly inhibits alpha interferon secretion, which may modulate the innate host response to the virus.