Replication, pathogenesis and transmission of pandemic (H1N1) 2009 virus in non-immune pigs.
Replication, pathogenesis and transmission of pandemic (H1N1) 2009 virus in non-immune pigs.
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DOI：
10.1371/journal.pone.0009068
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发表时间：
2010-02-05
期刊：
影响因子：
3.7
通讯作者：
Brown IH
中科院分区：
文献类型：
--
作者：
Brookes SM;Núñez A;Choudhury B;Matrosovich M;Essen SC;Clifford D;Slomka MJ;Kuntz-Simon G;Garcon F;Nash B;Hanna A;Heegaard PM;Quéguiner S;Chiapponi C;Bublot M;Garcia JM;Gardner R;Foni E;Loeffen W;Larsen L;Van Reeth K;Banks J;Irvine RM;Brown IH
2009年人类甲型流感（H1N1）大流行（H1N1/09）的宣布提出了重要问题，包括起源和宿主范围。上个世纪的三次大流行中有两次导致病毒传播到猪（H1N1，1918年; H3 N2，1968年），随后在全世界的猪中独立建立和进化。在不断演变的大流行背景下，一个关键的公共和兽医卫生考虑因素是H1N1/09病毒是否会在猪群中建立。我们在猪中进行了A/加州/07/09的感染和传播研究。结合临床、病理学、修饰的甲型流感病毒基质基因真实的时间RT-PCR和病毒基因组分析显示，感染导致诱导临床体征、局限于呼吸道的病毒发病机制、与猪中的甲型流感流行株一致的感染动力学、猪之间的病毒传播性和病毒-宿主适应事件。我们的研究结果表明，现存的H1N1/09完全有能力在全球猪群中建立。我们还显示了病毒受体特异性在传播和组织嗜性中的作用。值得注意的是，直接接种后的猪与病毒准种不同的氨基酸取代的血凝素受体结合位点，只有天冬氨酸在位置225（225 D）的病毒在接触感染猪的鼻分泌物中检测到。相比之下，在直接接种猪的下呼吸道样本中，具有明显的肺部病理学，存在明显的甘氨酸（225 G）病毒变体选择。这些发现为1918年大流行期间病毒受体结合变体225 D和225 G的存在和生物学意义提供了潜在的线索。
The declaration of the human influenza A pandemic (H1N1) 2009 (H1N1/09) raised important questions, including origin and host range. Two of the three pandemics in the last century resulted in the spread of virus to pigs (H1N1, 1918; H3N2, 1968) with subsequent independent establishment and evolution within swine worldwide. A key public and veterinary health consideration in the context of the evolving pandemic is whether the H1N1/09 virus could become established in pig populations. We performed an infection and transmission study in pigs with A/California/07/09. In combination, clinical, pathological, modified influenza A matrix gene real time RT-PCR and viral genomic analyses have shown that infection results in the induction of clinical signs, viral pathogenesis restricted to the respiratory tract, infection dynamics consistent with endemic strains of influenza A in pigs, virus transmissibility between pigs and virus-host adaptation events. Our results demonstrate that extant H1N1/09 is fully capable of becoming established in global pig populations. We also show the roles of viral receptor specificity in both transmission and tissue tropism. Remarkably, following direct inoculation of pigs with virus quasispecies differing by amino acid substitutions in the haemagglutinin receptor-binding site, only virus with aspartic acid at position 225 (225D) was detected in nasal secretions of contact infected pigs. In contrast, in lower respiratory tract samples from directly inoculated pigs, with clearly demonstrable pulmonary pathology, there was apparent selection of a virus variant with glycine (225G). These findings provide potential clues to the existence and biological significance of viral receptor-binding variants with 225D and 225G during the 1918 pandemic.
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