ABSTRACT

Influenza A/H5N1 has circulated in Asia since 2003 and is now enzootic in many countries in that region. In Cambodia, the virus has circulated since 2004 and has intermittently infected humans. During this period, we have noted differences in the rate of infections in humans, potentially associated with the circulation of different viral clades. In particular, a reassortant clade 1.1.2 virus emerged in early 2013 and was associated with a dramatic increase in infections of humans (34 cases) until it was replaced by a clade 2.3.2.1c virus in early 2014. In contrast, only one infection of a human has been reported in the 6 years since the clade 2.3.2.1c virus became the dominant circulating virus. We selected three viruses to represent the main viral clades that have circulated in Cambodia (clade 1.1.2, clade 1.1.2 reassortant, and clade 2.3.2.1c), and we conducted experiments to assess the virulence and transmissibility of these viruses in avian (chicken, duck) and mammalian (ferret) models. Our results suggest that the clade 2.3.2.1c virus is more “avian-like,” with high virulence in both ducks and chickens, but there is no evidence of aerosol transmission of the virus from ducks to ferrets. In contrast, the two clade 1 viruses were less virulent in experimentally infected and contact ducks. However, evidence of chicken-to-ferret aerosol transmission was observed for both clade 1 viruses. The transmission experiments provide insights into clade-level differences that might explain the variation in A/H5N1 infections of humans observed in Cambodia and other settings.

 抽象的

A/H5N1 流感自 2003 年起在亚洲流行，目前在该地区许多国家流行。在柬埔寨，该病毒自2004年开始传播，并间歇性感染人类。在此期间，我们注意到人类感染率的差异，这可能与不同病毒分支的循环有关。特别是，一种重配分支 1.1.2 病毒于 2013 年初出现，与人类感染病例急剧增加有关（34 例），直到 2014 年初被分支 2.3.2.1c 病毒取代。相比之下，只有一种自进化枝2.3.2.1c病毒成为主要传播病毒以来的6年里，已有人类感染的报道。我们选择了三种病毒来代表在柬埔寨传播的主要病毒分支（分支1.1.2、分支1.1.2重配和分支2.3.2.1c），并进行了实验来评估这些病毒在禽类中的毒力和传播性（鸡、鸭）和哺乳动物（雪貂）模型。我们的结果表明，进化枝 2.3.2.1c 病毒更像“禽类”，在鸭和鸡中具有高毒力，但没有证据表明该病毒通过气溶胶从鸭传播到雪貂。相比之下，两种1型病毒在实验感染和接触鸭中的毒性较低。然而，对于两种 1 分支病毒均观察到鸡到雪貂气溶胶传播的证据。传播实验提供了对进化枝水平差异的深入了解，这可能解释了在柬埔寨和其他地区观察到的人类 A/H5N1 感染的变化。