Chicken and duck myotubes are highly susceptible and permissive to influenza virus infection.
Chicken and duck myotubes are highly susceptible and permissive to influenza virus infection.
复制标题
DOI：
10.1128/jvi.03421-14
复制
发表时间：
2015-03
影响因子：
5.4
通讯作者：
Chang KC
中科院分区：
文献类型：
--
作者：
Baquero-Perez B;Kuchipudi SV;Ho J;Sebastian S;Puranik A;Howard W;Brookes SM;Brown IH;Chang KC
骨骼肌占体重的 30% 至 40%，是体内最丰富的软组织。除了运动和姿势的主要功能外，骨骼肌还是重要的先天免疫器官，能够产生细胞因子和趋化因子并对促炎细胞因子做出反应。关于骨骼肌在任何宿主（尤其是鸟类）全身性甲型流感病毒感染过程中的作用知之甚少。在这里，我们使用原代鸡和鸭多核肌管来检查它们对流感病毒感染的易感性和先天免疫反应。鸡和鸭的肌管均表达禽类和人类唾液酸受体，并且很容易受到低致病性（H2N3 A/绿头鸭/英格兰/7277/06）和高致病性（H5N1 A/火鸡/英格兰/50-92/91和H5N1 A/火鸡/土耳其/1/05）禽类和人类H1N1（A/USSR/77）的影响。流感病毒。两种鸟类宿主物种产生的后代 H5N1 A/turkey/Turkey/1/05 病毒水平相当。值得注意的是，病毒核蛋白和基质 (M) 基因 RNA 在鸡和鸭肌管中的快速积累伴随着广泛的细胞病变损伤和明显的肌管细胞凋亡（广泛的微小泡、半胱天冬酶 3/7 激活和膜联蛋白 V 与质膜结合）。受感染的鸡肌管产生的促炎细胞因子水平明显高于相应的鸭细胞。此外，在感染H5N1病毒的鸡肌管中，与感染相应的H2N3病毒相比，干扰素β（IFN-β）和IFN诱导基因（包括黑色素瘤分化相关蛋白5（MDA-5）基因）的诱导相对较弱。我们的研究结果强调，禽类骨骼肌纤维能够有效复制流感病毒，并且是潜在的组织感染源。重要性 鸭子感染高致病性 H5N1 病毒通常是无症状的，此类鸟类的骨骼肌可能是人类和动物的感染源。人们对甲型流感病毒在禽类骨骼肌纤维中复制的能力知之甚少。我们在此表明，培养的鸡和鸭肌管非常容易感染低致病性和高致病性禽流感病毒。两种鸟类受感染的肌管均表现出病毒快速积累、细胞凋亡和广泛的细胞损伤。我们的研究结果表明，鸡和鸭的禽类骨骼肌纤维可能对高致病性 H5N1 病毒的后代产生有重要贡献。
Skeletal muscle, at 30 to 40% of body mass, is the most abundant soft tissue in the body. Besides its primary function in movement and posture, skeletal muscle is a significant innate immune organ with the capacity to produce cytokines and chemokines and respond to proinflammatory cytokines. Little is known about the role of skeletal muscle during systemic influenza A virus infection in any host and particularly avian species. Here we used primary chicken and duck multinucleated myotubes to examine their susceptibility and innate immune response to influenza virus infections. Both chicken and duck myotubes expressed avian and human sialic acid receptors and were readily susceptible to low-pathogenicity (H2N3 A/mallard duck/England/7277/06) and high-pathogenicity (H5N1 A/turkey/England/50-92/91 and H5N1 A/turkey/Turkey/1/05) avian and human H1N1 (A/USSR/77) influenza viruses. Both avian host species produced comparable levels of progeny H5N1 A/turkey/Turkey/1/05 virus. Notably, the rapid accumulation of viral nucleoprotein and matrix (M) gene RNA in chicken and duck myotubes was accompanied by extensive cytopathic damage with marked myotube apoptosis (widespread microscopic blebs, caspase 3/7 activation, and annexin V binding at the plasma membrane). Infected chicken myotubes produced significantly higher levels of proinflammatory cytokines than did the corresponding duck cells. Additionally, in chicken myotubes infected with H5N1 viruses, the induction of interferon beta (IFN-β) and IFN-inducible genes, including the melanoma differentiation-associated protein 5 (MDA-5) gene, was relatively weak compared to infection with the corresponding H2N3 virus. Our findings highlight that avian skeletal muscle fibers are capable of productive influenza virus replication and are a potential tissue source of infection. IMPORTANCE Infection with high-pathogenicity H5N1 viruses in ducks is often asymptomatic, and skeletal muscle from such birds could be a source of infection of humans and animals. Little is known about the ability of influenza A viruses to replicate in avian skeletal muscle fibers. We show here that cultured chicken and duck myotubes were highly susceptible to infection with both low- and high-pathogenicity avian influenza viruses. Infected myotubes of both avian species displayed rapid virus accumulation, apoptosis, and extensive cellular damage. Our results indicate that avian skeletal muscle fibers of chicken and duck could be significant contributors to progeny production of highly pathogenic H5N1 viruses.