Long-term adaptation following influenza A virus host shifts results in increased within-host viral fitness due to higher replication rates, broader dissemination within the respiratory epithelium and reduced tissue damage.
Long-term adaptation following influenza A virus host shifts results in increased within-host viral fitness due to higher replication rates, broader dissemination within the respiratory epithelium and reduced tissue damage.
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甲型流感病毒宿主转移后的长期适应导致宿主内病毒适应性增强，这是由于复制率更高、呼吸道上皮内更广泛传播和组织损伤减少。
DOI：
10.1371/journal.ppat.1010174
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发表时间：
2021-12
期刊：
影响因子：
6.7
通讯作者：
Murcia PR
中科院分区：
文献类型：
--
作者：
Amat JAR;Patton V;Chauché C;Goldfarb D;Crispell J;Gu Q;Coburn AM;Gonzalez G;Mair D;Tong L;Martinez-Sobrido L;Marshall JF;Marchesi F;Murcia PR
基因组进化的机制和后果对病毒适应性后，主机转移知之甚少。此外，病毒适应性-生物体繁殖和生存的能力-是多因素的，因此难以量化。甲型流感病毒（IAV）在野鸟中广泛传播，并已在多种哺乳动物宿主中流行，包括人、猪、狗、海豹和马。H3 N8马流感病毒（EIV）是一种马的地方性病毒，起源于鸟类，自20世纪60年代初以来一直在马种群中不间断地传播。在这里，我们使用EIV来量化与病毒适应性相关的感染表型变化，这是由于在长期适应过程中获得的全基因组变化。我们使用最早分离的H3 N8 EIV（A/equine/Uruguay/63 [EIV/63]）和A/equine/俄亥俄州/2003（EIV/2003）（H3 N8 EIV出现40年后分离的EIV/63的单系后代）对两种哺乳动物细胞系和马气管外植体进行了实验感染。我们发现EIV/2003表现出对干扰素的抗性增加，病毒复制增强，以及在细胞和组织中更有效的细胞间传播。转录组学分析揭示了对每种病毒的病毒特异性反应，主要影响宿主免疫和炎症。感染的马呼吸道外植体的图像分析表明，尽管复制水平较高，并在呼吸道上皮的较大面积上传播，但与EIV/63相比，EIV/2003诱导的病变较轻，表明适应导致组织致病性降低。我们的研究结果揭示了病毒基因型和宿主对感染的反应之间先前未知的联系，为病毒进化和适应性之间的关系提供了新的见解。由于病毒是专性细胞内病原体，它们在宿主体内复制和传播的能力是生存的关键，即使它会导致宿主的严重疾病或死亡。了解病毒出现后病毒长期适应的后果是大流行防范的关键。H3 N8马流感病毒（EIV）起源于鸟类，自1963年以来一直在马中传播，因此为研究病毒适应性提供了独特的机会。我们比较了两种EIV的复制动力学相同的血统，但不同的进化历史：最早的病毒（EIV/63，分离于1963年），和EIV/2003，这是分离后40年的连续循环在马。细胞系（MDCK和E.Derm细胞）和马呼吸道外植体的实验感染表明，EIV朝着增强复制和细胞间传播的方向发展;但减少了组织损伤，证实了病毒适应性是适应性的，不一定导致更高的毒力。
The mechanisms and consequences of genome evolution on viral fitness following host shifts are poorly understood. In addition, viral fitness -the ability of an organism to reproduce and survive- is multifactorial and thus difficult to quantify. Influenza A viruses (IAVs) circulate broadly among wild birds and have jumped into and become endemic in multiple mammalian hosts, including humans, pigs, dogs, seals, and horses. H3N8 equine influenza virus (EIV) is an endemic virus of horses that originated in birds and has been circulating uninterruptedly in equine populations since the early 1960s. Here, we used EIV to quantify changes in infection phenotype associated to viral fitness due to genome-wide changes acquired during long-term adaptation. We performed experimental infections of two mammalian cell lines and equine tracheal explants using the earliest H3N8 EIV isolated (A/equine/Uruguay/63 [EIV/63]), and A/equine/Ohio/2003 (EIV/2003), a monophyletic descendant of EIV/63 isolated 40 years after the emergence of H3N8 EIV. We show that EIV/2003 exhibits increased resistance to interferon, enhanced viral replication, and a more efficient cell-to-cell spread in cells and tissues. Transcriptomics analyses revealed virus-specific responses to each virus, mainly affecting host immunity and inflammation. Image analyses of infected equine respiratory explants showed that despite replicating at higher levels and spreading over larger areas of the respiratory epithelium, EIV/2003 induced milder lesions compared to EIV/63, suggesting that adaptation led to reduced tissue pathogenicity. Our results reveal previously unknown links between virus genotype and the host response to infection, providing new insights on the relationship between virus evolution and fitness. As viruses are obligate intracellular pathogens, their ability to replicate and spread within their hosts is key for survival, even if it leads to severe disease or death of the host. Understanding the consequences of long-term virus adaptation after viral emergence is key for pandemic preparedness. H3N8 equine influenza virus (EIV) originated in birds and has circulated in horses since 1963, thus providing unique opportunities to study virus adaptation. We compared the replication kinetics of two EIVs of the same lineage but with different evolutionary histories: the earliest virus (EIV/63, isolated in 1963), and EIV/2003, which was isolated after 40 years of continuous circulation in horses. Experimental infections of cell lines (MDCK and E.Derm cells) and equine respiratory explants show that EIV evolved towards enhanced replication and cell-to-cell spread; but reduced tissue damage, confirming that viral fitness is adaptive and does not necessarily result in higher virulence.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
6.4
作者：
Checkmahomed, Liva;M'hamdi, Zeineb;Boivin, Guy
通讯作者：
Boivin, Guy
影响因子：
11.8
作者：
Bravo-Vasquez N;Yao J;Jimenez-Bluhm P;Meliopoulos V;Freiden P;Sharp B;Estrada L;Davis A;Cherry S;Livingston B;Danner A;Schultz-Cherry S;Hamilton-West C
通讯作者：
Hamilton-West C
影响因子：
6.4
作者：
Borisevich, Viktoriya;Lee, Benhur;Rockx, Barry
通讯作者：
Rockx, Barry
DOI：
10.1093/infdis/jiab147
发表时间：
2021-07-02
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Dee K;Goldfarb DM;Haney J;Amat JAR;Herder V;Stewart M;Szemiel AM;Baguelin M;Murcia PR
通讯作者：
Murcia PR