Lau Susanna K P, Woo Patrick C Y, Li Kenneth S M, Zhang Hao-Ji, Fan Rachel Y Y, Zhang Anna J X, Chan Brandon C C, Lam Carol S F, Yip Cyril C Y, Yuen Ming-Chi, Chan Kwok-Hung, Chen Zhi-Wei, Yuen Kwok-Yung
State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.
Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
PLoS Pathog. 2016 Oct 13;12(10):e1005911. doi: 10.1371/journal.ppat.1005911. eCollection 2016 Oct.
While novel picornaviruses are being discovered in rodents, their host range and pathogenicity are largely unknown. We identified two novel picornaviruses, rosavirus B from the street rat, Norway rat, and rosavirus C from five different wild rat species (chestnut spiny rat, greater bandicoot rat, Indochinese forest rat, roof rat and Coxing's white-bellied rat) in China. Analysis of 13 complete genome sequences showed that "Rosavirus B" and "Rosavirus C" represent two potentially novel picornavirus species infecting different rodents. Though being most closely related to rosavirus A, rosavirus B and C possessed distinct protease cleavage sites and variations in Yn-Xm-AUG sequence in 5'UTR and myristylation site in VP4. Anti-rosavirus B VP1 antibodies were detected in Norway rats, whereas anti-rosavirus C VP1 and neutralizing antibodies were detected in Indochinese forest rats and Coxing's white-bellied rats. While the highest prevalence was observed in Coxing's white-bellied rats by RT-PCR, the detection of rosavirus C from different rat species suggests potential interspecies transmission. Rosavirus C isolated from 3T3 cells causes multisystemic diseases in a mouse model, with high viral loads and positive viral antigen expression in organs of infected mice after oral or intracerebral inoculation. Histological examination revealed alveolar fluid exudation, interstitial infiltration, alveolar fluid exudate and wall thickening in lungs, and hepatocyte degeneration and lymphocytic/monocytic inflammatory infiltrates with giant cell formation in liver sections of sacrificed mice. Since rosavirus A2 has been detected in fecal samples of children, further studies should elucidate the pathogenicity and emergence potential of different rosaviruses.
虽然在啮齿动物中不断发现新型小RNA病毒,但其宿主范围和致病性在很大程度上仍不清楚。我们在中国从褐家鼠(挪威大鼠)中鉴定出两种新型小RNA病毒,即玫瑰病毒B,以及从五种不同的野生大鼠物种(刺巢鼠、大长爪鼠、越南林鼠、屋顶鼠和海南白腹鼠)中鉴定出玫瑰病毒C。对13个完整基因组序列的分析表明,“玫瑰病毒B”和“玫瑰病毒C”代表两种可能感染不同啮齿动物的新型小RNA病毒物种。尽管玫瑰病毒B和C与玫瑰病毒A关系最为密切,但它们具有独特的蛋白酶切割位点,5'UTR中的Yn-Xm-AUG序列以及VP4中的肉豆蔻酰化位点存在变异。在挪威大鼠中检测到抗玫瑰病毒B VP1抗体,而在越南林鼠和海南白腹鼠中检测到抗玫瑰病毒C VP1抗体和中和抗体。虽然通过RT-PCR在海南白腹鼠中观察到最高的流行率,但从不同大鼠物种中检测到玫瑰病毒C表明存在潜在的种间传播。从3T3细胞中分离出的玫瑰病毒C在小鼠模型中引起多系统疾病,口服或脑内接种后,感染小鼠的器官中病毒载量高且病毒抗原表达呈阳性。组织学检查显示,处死小鼠的肺组织中有肺泡液渗出、间质浸润、肺泡液渗出物和肺泡壁增厚,肝脏切片中有肝细胞变性以及淋巴细胞/单核细胞炎性浸润并形成巨细胞。由于在儿童粪便样本中检测到了玫瑰病毒A2,因此进一步的研究应阐明不同玫瑰病毒的致病性和出现的可能性。