Ng Aylwin, 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):2095-2105. doi: 10.1099/0022-1317-82-9-2095.
Vaccinia virus (VV) gene A41L encodes an acidic protein with amino acid similarity to the 35 kDa protein of VV strain Lister, a soluble protein called vCKBP that binds CC chemokines, and to a protein from orf virus, called GIF, that binds GM-CSF and IL-2. However, despite the similarity, recombinant A41L protein was found not to bind these ligands or a variety of other chemoattractant molecules when tested using surface plasmon resonance. The A41L gene is expressed early and late during infection and encodes a 30 kDa protein that contains both N- and O-linked carbohydrate and is secreted from the infected cell. All 16 strains of VV and 2 strains of cowpox virus that were tested express the A41L protein, implying it has an important function for orthopoxviruses. Nonetheless, a VV strain Western Reserve deletion mutant lacking the A41L gene (vDeltaA41L) formed normal sized plaques and replicated to the same titre as wild-type and revertant viruses. The importance of the A41L protein in vivo was demonstrated in a mouse intradermal model in which infection with vDeltaA41L caused more severe lesions compared to wild-type and revertant viruses. Further examination in this model revealed that deletion of A41L enhanced clearance of infectious virus, suggesting that A41L expression reduces immunopathology. Consistent with this, histological examination of infected rabbit skin showed that the A41L protein could reduce the infiltration of inflammatory cells into the infected area. Together, these data suggest that the A41L protein constitutes a novel immunomodulatory protein.
痘苗病毒（VV）的A41L基因编码一种酸性蛋白，该蛋白与VV李斯特株的35 kDa蛋白、一种名为vCKBP的可结合CC趋化因子的可溶性蛋白以及一种来自羊口疮病毒的名为GIF的可结合GM - CSF和IL - 2的蛋白具有氨基酸相似性。然而，尽管存在相似性，但在使用表面等离子体共振进行测试时，发现重组A41L蛋白不结合这些配体或多种其他趋化分子。A41L基因在感染的早期和晚期均有表达，编码一种30 kDa的蛋白，该蛋白同时含有N - 连接和O - 连接的碳水化合物，并从受感染细胞中分泌出来。所测试的所有16株VV和2株牛痘病毒均表达A41L蛋白，这意味着它对正痘病毒具有重要功能。尽管如此，一株缺乏A41L基因的VV西储株缺失突变体（vDeltaA41L）形成的噬斑大小正常，并且复制到与野生型和回复病毒相同的滴度。在小鼠皮内模型中证明了A41L蛋白在体内的重要性，与野生型和回复病毒相比，用vDeltaA41L感染会导致更严重的病变。在该模型中的进一步研究表明，缺失A41L会增强感染性病毒的清除，这表明A41L的表达可减少免疫病理学。与此一致的是，对感染兔皮肤的组织学检查表明，A41L蛋白可减少炎症细胞向感染区域的浸润。总之，这些数据表明A41L蛋白构成一种新型免疫调节蛋白。
