Differences in influenza virus receptors in chickens and ducks: Implications for interspecies transmission.

Differences in influenza virus receptors in chickens and ducks: Implications for interspecies transmission.
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DOI:
10.4172/1747-0862.1000026
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发表时间:
2009-01-16
期刊:
Journal of molecular and genetic medicine : an international journal of biomedical research
影响因子:
--
通讯作者:
Dunham S
Dunham S
中科院分区:
其他
文献类型:
--
作者:
Kuchipudi SV;Nelli R;White GA;Bain M;Chang KC;Dunham S

文献摘要

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禽流感病毒被认为是导致人类流感大流行的关键因素。感染的主要决定因素是易感细胞上存在病毒血凝素能够结合的病毒受体。禽病毒优先与唾液酸α2,3-半乳糖(SAα2,3-Gal)连接的受体结合,而人类病毒株与唾液酸α2,6-半乳糖(SAα2,6-Gal)连接的受体结合。虽然鸭子是流感病毒的主要宿主,但它们通常对病毒感染的影响具有抵抗力,这与在鸡中经常观察到的严重疾病相反。为了了解受体的差异是否可能促成这一观察结果,我们使用凝集素组织化学、连锁特异性凝集素以及猪和禽流感病毒的受体结合测定,研究了鸭和鸡器官中流感受体的分布。尽管这两个物种的肠上皮细胞仅表达SAα2,3-Gal受体,但我们发现在鸡和鸭的许多器官中广泛存在SAα2,6-Gal和SAα2,3-Gal受体。两种受体的共表达可能允许禽类和人类病毒感染细胞,因此提供了一条基因重排的途径。鸡和鸭气管的主要受体类型存在显着差异。在鸡气管中,SAα2,6-Gal 是主要受体类型,而在鸭中 SAα2,3-Gal 受体最丰富。这表明鸡作为流感病毒产生的中间宿主可能更为重要,其与 SAα2,6-Gal 受体结合的能力增强,因此感染人类的​​可能性更大。与鸭相比,鸡气管和肠上皮细胞还表达更广泛的 SAα2,3-Gal 受体(β(1-4)GlcNAc 和 β(1-3)GalNAc 亚型),这表明它们可能能够支持更广泛的禽流感病毒感染。
Avian influenza viruses are considered to be key contributors to the emergence of human influenza pandemics. A major determinant of infection is the presence of virus receptors on susceptible cells to which the viral haemagglutinin is able to bind. Avian viruses preferentially bind to sialic acid α2,3-galactose (SAα2,3-Gal) linked receptors, whereas human strains bind to sialic acid α2,6-galactose (SAα2,6-Gal) linked receptors. While ducks are the major reservoir for influenza viruses, they are typically resistant to the effects of viral infection, in contrast to the frequently severe disease observed in chickens. In order to understand whether differences in receptors might contribute to this observation, we studied the distribution of influenza receptors in organs of ducks and chickens using lectin histochemistry with linkage specific lectins and receptor binding assays with swine and avian influenza viruses. Although the intestinal epithelial cells of both species expressed only SAα2,3-Gal receptors, we found widespread presence of both SAα2,6-Gal and SAα2,3-Gal receptors in many organs of both chickens and ducks. Co-expression of both receptors may allow infection of cells with both avian and human viruses and so present a route to genetic reassortment. There was a marked difference in the primary receptor type in the trachea of chickens and ducks. In chicken trachea, SAα2,6-Gal was the dominant receptor type whereas in ducks SAα2,3-Gal receptors were most abundant. This suggests that chickens could be more important as an intermediate host for the generation of influenza viruses with increased ability to bind to SAα2,6-Gal receptors and thus greater potential for infection of humans. Chicken tracheal and intestinal epithelial cells also expressed a broader range of SAα2,3-Gal receptors (both β(1-4)GlcNAc and β(1-3)GalNAc subtypes) in contrast to ducks, which suggests that they may be able to support infection with a broader range of avian influenza viruses.