Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, Wisconsin, United States of America ; Wisconsin National Primate Research Center, Madison, Wisconsin, United States of America ; University of Wisconsin Microbiology Doctoral Training Program, Madison, Wisconsin, United States of America.
PLoS One. 2013 Nov 14;8(11):e78750. doi: 10.1371/journal.pone.0078750. eCollection 2013.
Studies of influenza transmission are necessary to predict the pandemic potential of emerging influenza viruses. Currently, both ferrets and guinea pigs are used in such studies, but these species are distantly related to humans. Nonhuman primates (NHP) share a close phylogenetic relationship with humans and may provide an enhanced means to model the virological and immunological events in influenza virus transmission. Here, for the first time, it was demonstrated that a human influenza virus isolate can productively infect and be transmitted between common marmosets (Callithrix jacchus), a New World monkey species. We inoculated four marmosets with the 2009 pandemic virus A/California/07/2009 (H1N1pdm) and housed each together with a naïve cage mate. We collected bronchoalveolar lavage and nasal wash samples from all animals at regular intervals for three weeks post-inoculation to track virus replication and sequence evolution. The unadapted 2009 H1N1pdm virus replicated to high titers in all four index animals by 1 day post-infection. Infected animals seroconverted and presented human-like symptoms including sneezing, nasal discharge, labored breathing, and lung damage. Transmission occurred in one cohabitating pair. Deep sequencing detected relatively few genetic changes in H1N1pdm viruses replicating in any infected animal. Together our data suggest that human H1N1pdm viruses require little adaptation to replicate and cause disease in marmosets, and that these viruses can be transmitted between animals. Marmosets may therefore be a viable model for studying influenza virus transmission.
流感传播的研究对于预测新出现的流感病毒的大流行潜力是必要的。目前,雪貂和豚鼠都被用于此类研究,但这些物种与人类的亲缘关系较远。非人类灵长类动物(NHP)与人类具有密切的系统发育关系,可能为模拟流感病毒传播中的病毒学和免疫学事件提供增强的手段。在这里,首次证明了一种人源流感病毒分离株可以在新世界猴(Callithrix jacchus)中有效感染和传播。我们用 2009 年大流行病毒 A/加利福尼亚/07/2009(H1N1pdm)对四只绒猴进行了接种,并将每只与一只未感染的笼伴放在一起。我们在接种后三周内定期从所有动物中采集支气管肺泡灌洗液和鼻洗液样本,以追踪病毒复制和序列进化。未适应的 2009 年 H1N1pdm 病毒在所有四只指数动物中在感染后 1 天内复制到高滴度。感染动物血清转化并出现打喷嚏、鼻漏、呼吸困难和肺部损伤等类似人类的症状。在一对同居的动物中发生了传播。深度测序检测到在任何感染动物中复制的 H1N1pdm 病毒的遗传变化相对较少。我们的数据表明,人源 H1N1pdm 病毒在绒猴中复制和引起疾病需要很少的适应,并且这些病毒可以在动物之间传播。因此,绒猴可能是研究流感病毒传播的可行模型。