Genetics, Receptor Binding, Replication, and Mammalian Transmission of H4 Avian Influenza Viruses Isolated from Live Poultry Markets in China.
Genetics, Receptor Binding, Replication, and Mammalian Transmission of H4 Avian Influenza Viruses Isolated from Live Poultry Markets in China.
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DOI：
10.1128/jvi.02692-15
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发表时间：
2016-02-01
影响因子：
5.4
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Liang L;Deng G;Shi J;Wang S;Zhang Q;Kong H;Gu C;Guan Y;Suzuki Y;Li Y;Jiang Y;Tian G;Liu L;Li C;Chen H
H4 禽流感病毒 (AIV) 是世界上最流行的流感病毒亚型之一。然而，H4 AIV 是否对公众健康构成威胁目前尚不清楚。在此，我们分析了 2009 年至 2012 年间从中国活禽市场分离的 H4 型 AIV 病毒的系统发育关系、受体结合特性、复制和在哺乳动物中的传播性。对 36 种代表性 H4 病毒的基因组序列分析揭示了 32 种不同的基因型，表明这些病毒正在经历复杂而频繁的重配事件。所有 32 种测试的病毒都可以在受感染小鼠的呼吸器官中复制，而无需事先适应。受体结合分析表明，H4 AIV 与 α-2,6-连接聚糖结合，尽管它们保留了对 α-2,3-连接聚糖的结合偏好。当我们测试10种H4病毒在豚鼠体内的直接接触传播时，我们发现三种病毒没有传播给任何接触动物，一种病毒传播给三只接触动物中的一只，六种病毒传播给所有三只接触动物。当我们进一步测试四种通过直接接触有效传播的病毒的呼吸道飞沫传播能力时，我们发现其中三种病毒可以传播给五只暴露动物中的一两只。我们的研究表明，当前流行的H4 AIV可以感染、复制并传播给哺乳动物宿主，从而对人类健康构成潜在威胁。这些发现强调需要持续加强对 H4 AIV 的监测。重要性 大量监测研究记录了 H4 AIV 在世界各地的广泛分布，但 H4 病毒的生物学特性尚未得到充分研究。在这项研究中，我们发现多种基因型的H4病毒在中国的活禽市场中共同传播，并且H4病毒可以在小鼠体内复制，具有人型受体结合特异性，并通过直接接触在豚鼠之间传播。引人注目的是，一些 H4 菌株也可以通过呼吸道飞沫传播，尽管效率有限。这些结果清楚地表明H4病毒对公众健康构成的潜在威胁。
H4 avian influenza virus (AIV) is one of the most prevalent influenza virus subtypes in the world. However, whether H4 AIVs pose a threat to public health remains largely unclear. Here, we analyzed the phylogenetic relationships, receptor binding properties, replication, and transmissibility in mammals of H4 AIVs isolated from live poultry markets in China between 2009 and 2012. Genomic sequence analysis of 36 representative H4 viruses revealed 32 different genotypes, indicating that these viruses are undergoing complex and frequent reassortment events. All 32 viruses tested could replicate in the respiratory organs of infected mice without prior adaptation. Receptor binding analysis demonstrated that the H4 AIVs bound to α-2,6-linked glycans, although they retained the binding preference for α-2,3-linked glycans. When we tested the direct-contact transmission of 10 H4 viruses in guinea pigs, we found that three viruses did not transmit to any of the contact animals, one virus transmitted to one of three contact animals, and six viruses transmitted to all three contact animals. When we further tested the respiratory droplet transmissibility of four of the viruses that transmitted efficiently via direct contact, we found that three of them could transmit to one or two of the five exposed animals. Our study demonstrates that the current circulating H4 AIVs can infect, replicate in, and transmit to mammalian hosts, thereby posing a potential threat to human health. These findings emphasize the continual need for enhanced surveillance of H4 AIVs. IMPORTANCE Numerous surveillance studies have documented the wide distribution of H4 AIVs throughout the world, yet the biological properties of H4 viruses have not been well studied. In this study, we found that multiple genotypes of H4 viruses are cocirculating in the live poultry markets of China and that H4 viruses can replicate in mice, possess human-type receptor binding specificity, and transmit between guinea pigs via direct contact. Strikingly, some H4 strains also can transmit via respiratory droplet, albeit with limited efficiency. These results clearly show the potential threat posed by H4 viruses to public health.