Feline morbillivirus, a previously undescribed paramyxovirus associated with tubulointerstitial nephritis in domestic cats
Feline morbillivirus, a previously undescribed paramyxovirus associated with tubulointerstitial nephritis in domestic cats
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DOI：
10.1073/pnas.1119972109
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发表时间：
2012-04-03
影响因子：
11.1
通讯作者：
Yuen, Kwok-Yung
中科院分区：
文献类型：
--
作者：
Woo, Patrick C. Y.;Lau, Susanna K. P.;Yuen, Kwok-Yung
本文报道了从家猫（Felis卡图斯）中发现并分离到的一种副粘病毒-猫麻疹病毒（FmoPV）。通过RT-PCR在457只流浪猫中的56只（12.3%）（53只尿液，4只直肠拭子和1份血液样本）中检测到FmoPV RNA。三个FmoPV株的全基因组测序显示基因组大小为16，050个碱基，这是麻疹病毒中最大的，因为异常长的400 nt的5'尾部序列。FmoPV具有相同的基因内容（3 '-N-P/V/C-M-F-H-L-5'），并且与其它麻疹病毒在染色体上聚为一簇。Westernblot检测56只RT-PCR阳性猫中49只（76.7%）血清抗FmoPV N蛋白IgG阳性，而401只RT-PCR阴性猫中78只（19.4%）血清抗FmoPV N蛋白IgG阳性（P < 0.0001）。从CRFK猫肾细胞中分离出FmoPV，引起细胞病变效应，包括细胞变圆、分离、溶解和合胞体形成。FmoPV也可以在灵长类动物Vero E6细胞中在随后的传代中复制。感染的细胞系表现出细颗粒和弥漫的细胞质荧光免疫染色的FmoPV N蛋白。电子显微镜下显示有包膜病毒，具有副粘病毒中典型的“人字形”螺旋N外观。对两只FmoPV阳性猫的尸检组织进行组织学检查，发现肾间质炎性浸润和肾小管变性/坏死，变性肾小管上皮细胞中的生长素表达降低，与肾小管间质性肾炎（TIN）相符。免疫组织化学染色显示，FmoPV N蛋白阳性肾小管细胞和淋巴结单核细胞。一项病例对照研究显示，在12只感染FmoPV的猫中有7只存在TIN，而在15只未感染FmoPV的猫中只有2只存在TIN（P < 0.05），表明FmoPV与TIN之间存在关联。
We describe the discovery and isolation of a paramyxovirus, feline morbillivirus (FmoPV), from domestic cat (Felis catus). FmoPV RNA was detected in 56 (12.3%) of 457 stray cats (53 urine, four rectal swabs, and one blood sample) by RT-PCR. Complete genome sequencing of three FmoPV strains showed genome sizes of 16,050 bases, the largest among morbilliviruses, because of unusually long 5' trailer sequences of 400 nt. FmoPV possesses identical gene contents (3'-N-P/V/C-M-F-H-L-5') and is phylogenetically clustered with other morbilliviruses. IgG against FmoPV N protein was positive in 49 sera (76.7%) of 56 RT-PCR-positive cats, but 78 (19.4%) of 401 RT-PCR-negative cats (P < 0.0001) by Western blot. FmoPV was isolated from CRFK feline kidney cells, causing cytopathic effects with cell rounding, detachment, lysis, and syncytia formation. FmoPV could also replicate in subsequent passages in primate Vero E6 cells. Infected cell lines exhibited finely granular and diffuse cytoplasmic fluorescence on immunostaining for FmoPV N protein. Electron microscopy showed enveloped virus with typical "herringbone" appearance of helical N in paramyxoviruses. Histological examination of necropsy tissues in two FmoPV-positive cats revealed interstitial inflammatory infiltrate and tubular degeneration/necrosis in kidneys, with decreased cauxin expression in degenerated tubular epithelial cells, compatible with tubulointerstitial nephritis (TIN). Immunohistochemical staining revealed FmoPV N protein-positive renal tubular cells and mononuclear cells in lymph nodes. A case-control study showed the presence of TIN in seven of 12 cats with FmoPV infection, but only two of 15 cats without FmoPV infection (P < 0.05), suggesting an association between FmoPV and TIN.