The r131 gene of rat cytomegalovirus encodes a proinflammatory CC chemokine homolog which is essential for the production of infectious virus in the salivary glands
The r131 gene of rat cytomegalovirus encodes a proinflammatory CC chemokine homolog which is essential for the production of infectious virus in the salivary glands
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DOI：
10.1023/b:viru.0000032788.53592.7c
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发表时间：
2004-08-01
期刊：
影响因子：
1.6
通讯作者：
Vink, C
中科院分区：
文献类型：
--
作者：
Kaptein, SJF;van Cleef, KWR;Vink, C
大鼠巨细胞病毒(RCMV)具有两个相邻的基因R131和R129，可能编码CC趋化因子同源物。有趣的是，这两个基因编码的氨基酸序列与由m131/129基因编码的小鼠CMV(MCMV)MCK-2蛋白的序列相似。为了研究RCMV R131基因在RCMV感染发病机制中的意义，我们产生了两种不同的病毒株，其中R131开放阅读框被打乱。对这些缺失突变株RCMVDeltar131a和RCMVDeltar131b的体外和体内复制进行了评价。两个毒株在体外的复制效率都与野生型(WT)RCMV相似。然而，与WT病毒相反，RCMVDr131a和RCMVDr131b都没有在免疫受损大鼠的唾液腺中建立高滴度感染。此外，在局部的大鼠足垫感染模型中，两种重组病毒引起的足爪肿胀量都明显低于WT RCMV。此外，感染WT RCMV的爪子比感染重组子的爪子有更多的巨噬细胞渗入。综上所述，这些结果表明，R131(I)促进了最初接种部位的炎症，随后有效地将病毒传播到唾液腺或感染唾液腺，以及(II)可能与病毒感染的持续有关，至少在脾内。此外，我们的数据表明，R131代表了MCMV m131/129基因的功能同源。
Rat cytomegalovirus ( RCMV) possesses two adjacent genes, r131 and r129, which have the potential to encode CC chemokine homologs. Interestingly, the amino acid sequences encoded by both genes show similarity to the sequence of the murine CMV (MCMV) MCK-2 protein, which is encoded by the m131/129 gene. In order to study the significance of the r131 gene in the pathogenesis of RCMV infection, we generated two different virus strains in which the r131 open reading frame is disrupted. Replication of these null mutant strains, designated RCMVDeltar131a and RCMVDeltar131b, was evaluated in vitro and in vivo. Both strains were found to replicate with a similar efficiency as wild-type (WT) RCMV in vitro. However, in contrast to WT virus, neither RCMVDr131a nor RCMVDr131b established a high-titer infection in the salivary glands of immunocompromised rats. Furthermore, in a local, rat footpad infection model, both recombinant viruses induced a significantly lower amount of paw swelling than did WT RCMV. Also, a higher number of infiltrating macrophages was observed in paws infected with WT RCMV than in those infected with the recombinants. Taken together, these results suggest that r131 (i) promotes inflammation at initial sites of inoculation and, subsequently, efficient virus dissemination to or infection of the salivary glands and (ii) might be involved in the persistence of virus infection, at least in the spleen. In addition, our data indicate that r131 represents the functional homolog of the MCMV m131/129 gene.