Canuti Marta, Williams Cathy V, Gadi Sashi R, Jebbink Maarten F, Oude Munnink Bas B, Jazaeri Farsani Seyed Mohammad, Cullen John M, van der Hoek Lia
Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam Amsterdam, Netherlands.
Duke Lemur Center, Duke University Durham, NC, USA.
Front Microbiol. 2014 Dec 1;5:655. doi: 10.3389/fmicb.2014.00655. eCollection 2014.
Cancer is one of the leading health concerns for human and animal health. Since the tumorigenesis process is not completely understood and it is known that some viruses can induce carcinogenesis, it is highly important to identify novel oncoviruses and extensively study underlying oncogenic mechanisms. Here, we investigated a case of diffuse histiocytic sarcoma in a 22 year old slow loris (Nycticebus coucang), using a broad spectrum virus discovery technique. A novel parvovirus was discovered and the phylogenetic analysis performed on its fully sequenced genome demonstrated that it represents the first member of a novel genus. The possible causative correlation between this virus and the malignancy was further investigated and 20 serum and 61 organ samples from 25 animals (N. coucang and N. pygmaeus) were screened for the novel virus but only samples collected from the originally infected animal were positive. The virus was present in all tested organs (intestine, liver, spleen, kidneys, and lungs) and in all banked serum samples collected up to 8 years before death. All attempts to identify a latent viral form (integrated or episomal) were unsuccessful and the increase of variation in the viral sequences during the years was consistent with absence of latency. Since it is well known that parvoviruses are dependent on cell division to successfully replicate, we hypothesized that the virus could have benefitted from the constantly dividing cancer cells and may not have been the cause of the histiocytic sarcoma. It is also possible to conjecture that the virus had a role in delaying the tumor progression and this report might bring new exciting opportunities in recognizing viruses to be used in cancer virotherapy.
癌症是人类和动物健康面临的主要健康问题之一。由于肿瘤发生过程尚未完全明了,且已知某些病毒可诱发癌症,因此鉴定新型致癌病毒并广泛研究其潜在致癌机制至关重要。在此,我们使用广谱病毒发现技术,对一只22岁懒猴(蜂猴)身上的弥漫性组织细胞肉瘤病例进行了调查。发现了一种新型细小病毒,对其全基因组测序进行的系统发育分析表明,它代表了一个新属的首个成员。进一步研究了该病毒与恶性肿瘤之间可能的因果关系,对来自25只动物(蜂猴和倭蜂猴)的20份血清和61份器官样本进行了新型病毒筛查,但仅最初感染动物的样本呈阳性。该病毒存在于所有测试器官(肠道、肝脏、脾脏、肾脏和肺)以及死亡前8年收集的所有保存血清样本中。所有鉴定潜伏病毒形式(整合或游离)的尝试均未成功,且多年来病毒序列变异的增加与潜伏的缺失一致。由于众所周知细小病毒依赖细胞分裂来成功复制,我们推测该病毒可能受益于不断分裂的癌细胞,可能并非组织细胞肉瘤的病因。也可以推测该病毒在延缓肿瘤进展方面发挥了作用,本报告可能为识别可用于癌症病毒疗法的病毒带来新的令人兴奋的机会。