Assessment of transmission, pathogenesis and adaptation of H2 subtype influenza viruses in ferrets
Assessment of transmission, pathogenesis and adaptation of H2 subtype influenza viruses in ferrets
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DOI：
10.1016/j.virol.2015.01.002
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发表时间：
2015-03-01
期刊：
影响因子：
3.7
通讯作者：
Tumpey, Terrence M.
中科院分区：
文献类型：
--
作者：
Pappas, Claudia;Yang, Hua;Tumpey, Terrence M.
自1968年从人类种群中消失后，流感H2病毒继续在天然禽类水库中传播。从多种禽类和猪中分离出该病毒亚型凸显了更好地了解这些病毒在人类中传播和致病的可能性的必要性。在这里，我们分析了两种禽流感H2病毒(H_2N_2和H_2N_3)的毒力、传播性和受体结合偏好，并以雪貂为宿主，将它们与猪H_2N_3病毒(A/swine/Misouri/2124514/2006)和人H_2N_2病毒(A/England/10/1967[Eng/67])进行了比较。两种禽类H2病毒均具有在群养雪貂之间有效传播的能力，而猪(SwMO)和人(Eng/67)病毒通过呼吸道飞沫传播给初代雪貂。通过X射线结晶学和葡聚糖微阵列阵列对swMO血凝素(HA)的进一步表征发现了受体特异性的适应性突变。由于流感病毒在传播过程中的准种动态尚未得到很好的表征，我们对传播研究期间收集的鼻液进行了测序，以更好地了解H2 HA的实验适应情况。从雪貂鼻水中分离的禽类H2病毒含有HA1突变，包括Gln226Leu替换，这是一种与2，6-唾液酸(类人)结合偏好相关的突变。这些结果表明，在获得额外的遗传标记后，H2亚型病毒中HA的分子结构继续具有适应哺乳动物宿主并变得可传播的潜力。由爱思唯尔公司出版。
After their disappearance from the human population in 1968, influenza H2 viruses have continued to circulate in the natural avian reservoir. The isolation of this virus subtype from multiple bird species as well as swine highlights the need to better understand the potential of these viruses to spread and cause disease in humans. Here we analyzed the virulence, transmissibility and receptor-binding preference of two avian influenza H2 viruses (H2N2 and H2N3) and compared them to a swine H2N3 (A/swine/Missouri/2124514/2006 [swMO]), and a human H2N2 (A/England/10/1967 [Eng/67]) virus using the ferret model as a mammalian host. Both avian H2 viruses possessed the capacity to spread efficiently between cohoused ferrets, and the swine (swMO) and human (Eng/67) viruses transmitted to nave ferrets by respiratory droplets. Further characterization of the swMO hemagglutinin (HA) by x-ray crystallography and glycan microarray array identified receptor-specific adaptive mutations. As influenza virus quasispecies dynamics during transmission have not been well characterized, we sequenced nasal washes collected during transmission studies to better understand experimental adaptation of H2 HA. The avian H2 viruses isolated from ferret nasal washes contained mutations in the HA1, including a Gln226Leu substitution, which is a mutation associated with 2,6 sialic acid (human-like) binding preference. These results suggest that the molecular structure of HA in viruses of the H2 subtype continue to have the potential to adapt to a mammalian host and become transmissible, after acquiring additional genetic markers. Published by Elsevier Inc.