新发现的老鼠病毒有望为未来肝炎的研究铺平道路,让科学家能最终实现在实验室利用动物模型进行人类疾病研究和疫苗的开发.科学家在冻存的野生型老鼠中寻找与人类丙型肝炎病毒(human hepatitis C virus,HCV)以及人类Pegiviruses病毒(HPgV)相关的病毒进行了研究,发现了几种新型的肝炎病毒(hepaciviruses) 和 pegiviruses与人类病毒有着十分近的亲缘关系,这暗示着可以在小鼠模型中实现相关疾病的研究,而不需要人类志愿者.

虽然大约有2%的人感染了丙肝病毒,5%的人感染了HPgV,但是很难进行新药物和疫苗的研发,因为侵染人类的病毒并不侵染实验室研究所用的模式动物.美国哥伦比亚大学的Amit Kapoor 说,能在老鼠体内发现与人类病毒相似的病毒让他感到很惊讶.

“人们等这一结果已经等了几十年.我很惊讶能发现这些病毒,而且还有那么多.” Kapoor说.

为了能在动物体内寻找到与人类丙肝病毒和HPgV有亲缘关系的病毒,Kapoor及其同事筛选了超过400个所保存的冻啮齿动物,大部分是鹿鼠.他们找到了很多候选病毒,然后从中选择了2种进行全基因组测序：一种是存在于鹿鼠中的啮齿动物hepacivirus（RHV）,另一种是存在于林鼠中的啮齿动物pegivirus(RPgV).测序结果进一步证实了这些病毒与人类相关疾病的病毒具有极高的亲缘关系,但是它们属于Flaviviridae家族中的新成员.

这些啮齿动物病毒拥有与人类hepaciviruses 和 pegiviruses相似的基因、蛋白和转录元件,暗示着这些病毒具有极高的实验室研究潜力.能进行肝炎研究的动物模型可以帮助科学家探索这些病毒是如何引发疾病的,从而有利于新治疗方法及疫苗的研发.另一方面,HPgV的功能仍是不明的,所以在啮齿动物中研究它们是如何起作用的,可以了解这类病毒在人体内的作用方式,同时还能了解为什么那么多人会感染此类病毒.

现在,Kapoor的研究室专注于探索这些病毒的生物学特性.“我们正努力尝试让鹿鼠感染,这样就能研究这种类丙肝病毒的生物特性.”Kapoor说,“如果我们发现这些病毒对肝脏有亲和性,并且能引起与丙肝相似的症状,那这就向了解人类丙肝病毒诱导病理迈进了一大步.”（生物谷Bioon.com）

doi: 10.1128/?mBio.00216-13PMC:PMID:

Identification of Rodent Homologs of Hepatitis C Virus and Pegiviruses

Amit Kapoora, Peter Simmondsb, Troels K. H. Scheelc,d, Brian Hjellee, John M. Cullenf, Peter D. Burbelog, Lokendra V. Chauhana, Raja Duraisamya, Maria Sanchez Leona, Komal Jaina, Kurt Jason Vandegrifth, Charles H. Calishera, Charles M. Ricec, W. Ian Lipkina

Hepatitis C virus (HCV) and human pegivirus (HPgV or GB virus C) are globally distributed and infect 2 to 5% of the human population. The lack of tractable-animal models for these viruses, in particular for HCV, has hampered the study of infection, transmission, virulence, immunity, and pathogenesis. To address this challenge, we searched for homologous viruses in small mammals, including wild rodents. Here we report the discovery of several new hepaciviruses (HCV-like viruses) and pegiviruses (GB virus-like viruses) that infect wild rodents. Complete genome sequences were acquired for a rodent hepacivirus (RHV) found in Peromyscus maniculatus and a rodent pegivirus (RPgV) found in Neotoma albigula. Unique genomic features and phylogenetic analyses confirmed that these RHV and RPgV variants represent several novel virus species in the Hepacivirus and Pegivirus genera within the family Flaviviridae. The genetic diversity of the rodent hepaciviruses exceeded that observed for hepaciviruses infecting either humans or non-primates, leading to new insights into the origin, evolution, and host range of hepaciviruses. The presence of genes, encoded proteins, and translation elements homologous to those found in human hepaciviruses and pegiviruses suggests the potential for the development of new animal systems with which to model HCV pathogenesis, vaccine design, and treatment.

IMPORTANCE The genetic and biological characterization of animal homologs of human viruses provides insights into the origins of human infections and enhances our ability to study their pathogenesis and explore preventive and therapeutic interventions. Horses are the only reported host of nonprimate homologs o