Gardner Jeremy D, Tscharke David C, Reading Patrick C, Smith Geoffrey L
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK1.
J Gen Virol. 2001 Sep;82(Pt 9):2083-2093. doi: 10.1099/0022-1317-82-9-2083.
Vaccinia virus (VV) protein A39R has amino acid similarity to the extracellular domain of a glycosylphosphatidylinositol-linked cell surface semaphorin (SEMA7A/CDw108) that has an immunological expression profile and binding properties, thereby implicating A39R as an immunomodulator. Previously, a closely related A39R protein expressed by ectromelia virus was shown to induce cytokine production and up-regulate ICAM-1 expression in mouse monocytes in vitro. In this study, we show that the A39R gene of VV strain Copenhagen (COP) encodes a 50-55 kDa secreted glycoprotein and is expressed late during infection. The A39R protein was secreted by eight of 15 strains of VV, but not by strain Western Reserve (WR). To analyse the VV A39R function, several recombinant viruses were made, including an A39R deletion mutant of VV COP and a WR mutant containing the A39R sequence from COP. Loss of the gene from COP did not affect virus growth in vitro, or VV virulence in a mouse intranasal model, and had only a slight effect on lesion size in an intradermal model. In contrast, expression of COP A39R by VV WR was associated with an increase in the severity and persistence of skin lesions after intradermal infection of mice. Finally, a histological examination of mouse skin infected with recombinant viruses suggested that A39R has direct or indirect pro-inflammatory properties.
痘苗病毒（VV）的A39R蛋白与糖基磷脂酰肌醇连接的细胞表面信号素（SEMA7A/CDw108）的胞外结构域具有氨基酸相似性，该信号素具有免疫表达谱和结合特性，因此表明A39R是一种免疫调节剂。此前，已证明由埃可病毒表达的一种密切相关的A39R蛋白可在体外诱导小鼠单核细胞产生细胞因子并上调ICAM-1的表达。在本研究中，我们发现痘苗病毒哥本哈根株（COP）的A39R基因编码一种50-55 kDa的分泌型糖蛋白，且在感染后期表达。15株痘苗病毒中有8株分泌A39R蛋白，但西储株（WR）不分泌。为了分析痘苗病毒A39R的功能，构建了几种重组病毒，包括痘苗病毒COP的A39R缺失突变体和含有COP的A39R序列的WR突变体。COP缺失该基因不影响其体外生长，也不影响其在小鼠鼻内模型中的毒力，对皮内模型中的损伤大小只有轻微影响。相反，痘苗病毒WR表达COP的A39R与小鼠皮内感染后皮肤损伤的严重程度和持续时间增加有关。最后，对感染重组病毒的小鼠皮肤进行组织学检查表明，A39R具有直接或间接的促炎特性。
