Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways

Scull, Margaret A.; Gillim-Ross, Laura; Santos, Celia; Roberts, Kim L.; Bordonali, Elena; Subbarao, Kanta; Barclay, William; Pickles, Raymond J.

doi:10.1371/journal.ppat.1000424

Cited by 72 publications

(78 citation statements)

References 52 publications

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“…A strain with relatively poor persistence at high temperatures could be assumed [31] to fare poorly during infection within a host, where internal temperatures can be high (e.g. 408C inside a duck [54,55]). …”

Section: Results (A) Quantifying Temperature-dependent Environmental mentioning

confidence: 99%

Trade-offs between and within scales: environmental persistence and within-host fitness of avian influenza viruses

et al. 2014

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Trade-offs between different components of a pathogen's replication and transmission cycle are thought to be common. A number of studies have identified trade-offs that emerge across scales, reflecting the tension between strategies that optimize within-host proliferation and large-scale population spread. Most of these studies are theoretical in nature, with direct experimental tests of such cross-scale trade-offs still rare. Here, we report an analysis of avian influenza A viruses across scales, focusing on the phenotype of temperaturedependent viral persistence. Taking advantage of a unique dataset that reports both environmental virus decay rates and strain-specific viral kinetics from duck challenge experiments, we show that the temperature-dependent environmental decay rate of a strain does not impact within-host virus load. Hence, for this phenotype, the scales of within-host infection dynamics and between-host environmental persistence do not seem to interact: viral fitness may be optimized on each scale without cross-scale trade-offs. Instead, we confirm the existence of a temperature-dependent persistence trade-off on a single scale, with some strains favouring environmental persistence in water at low temperatures while others reduce sensitivity to increasing temperatures. We show that this temperature-dependent trade-off is a robust phenomenon and does not depend on the details of data analysis. Our findings suggest that viruses might employ different environmental persistence strategies, which facilitates the coexistence of diverse strains in ecological niches. We conclude that a better understanding of the transmission and evolutionary dynamics of influenza A viruses probably requires empirical information regarding both within-host dynamics and environmental traits, integrated within a combined ecological and within-host framework.

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Section: Results (A) Quantifying Temperature-dependent Environmental mentioning

confidence: 99%

Trade-offs between and within scales: environmental persistence and within-host fitness of avian influenza viruses

et al. 2014

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“…Unlike human influenza viruses, which replicate efficiently in respiratory tracts where the temperatures range from 32°C in the upper respiratory tract to 37°C in lower respiratory tract (34,35), avian influenza viruses have adapted to replicate at the higher temperatures, 40 to 41°C, of the avian enteric tract (36). The upper respiratory tract provides a large surface area of susceptible cells and is usually the initial site of infection and likely the predominant site of influenza virus replication in mammalian species (37).…”

Section: Figmentioning

confidence: 99%

“…Scull et al demonstrated that amino acid substitution Glu627Lys in PB2 does not entirely account for conferring temperature dependency in mammalian cells. It was suggested that viruses bearing avian or avianlike surface glycoproteins have a reduced capacity to establish productive infection at the temperature of the human proximal airways (36).…”

Section: Figmentioning

confidence: 99%

Pathogenesis and Transmission of Novel Highly Pathogenic Avian Influenza H5N2 and H5N8 Viruses in Ferrets and Mice

Pulit-Penaloza

Sun

Creager

et al. 2015

J Virol

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A novel highly pathogenic avian influenza (HPAI) H5N8 virus, first detected in January 2014 in poultry and wild birds in South Korea, has spread throughout Asia and Europe and caused outbreaks in Canada and the United States by the end of the year. The spread of H5N8 and the novel reassortant viruses, H5N2 and H5N1 (H5Nx), in domestic poultry across multiple states in the United States pose a potential public health risk. To evaluate the potential of cross-species infection, we determined the pathogenicity and transmissibility of two Asian-origin H5Nx viruses in mammalian animal models. The newly isolated H5N2 and H5N8 viruses were able to cause severe disease in mice only at high doses. Both viruses replicated efficiently in the upper and lower respiratory tracts of ferrets; however, the clinical symptoms were generally mild, and there was no evidence of systemic dissemination of virus to multiple organs. Moreover, these influenza H5Nx viruses lacked the ability to transmit between ferrets in a direct contact setting. We further assessed viral replication kinetics of the novel H5Nx viruses in a human bronchial epithelium cell line, Calu-3. Both H5Nx viruses replicated to a level comparable to a human seasonal H1N1 virus, but significantly lower than a virulent Asian-lineage H5N1 HPAI virus. Although the recently isolated H5N2 and H5N8 viruses displayed moderate pathogenicity in mammalian models, their ability to rapidly spread among avian species, reassort, and generate novel strains underscores the need for continued risk assessment in mammals. O n 16 December 2014, the U.S. Department of Agriculture (USDA) confirmed the presence of a novel highly pathogenic avian influenza (HPAI) H5N8 virus in a captive gyrfalcon and H5N2 virus in a northern pintail duck from Whatcom County, Washington (1). This represented the first appearance of HPAI H5 virus in the United States since 2004 when H5N2 subtype virus was confirmed on a poultry farm in Texas (2). HPAI H5N8 viruses were first reported in duck farms in eastern China in 2010, and in early 2014 a novel reassortant H5N8 virus was detected in poultry in South Korea (3-5). The novel virus, belonging to Eurasian lineage clade 2.3.4.4 (formerly clade 2.3.4.6), subsequently spread to China, Japan, and five countries in Europe (6, 7). In November 2014, the virus was detected on chicken and turkey farms in British Columbia, Canada, followed by Washington State, USA, the following month (8). The novel H5N8 viruses continue to spread to multiple regions and have been found in three North America flyways (Pacific, Central, and Mississippi), where wild-bird migrations occur (USDA, Animal and Plant Health Inspection Service [http://www.aphis.usda.gov]). In addition, genetic reassortment with circulating North American avian influenza viruses has resulted in novel HPAI viruses, including H5N2 and H5N1 subtypes. These novel reassortant viruses carry a Eurasian-origin hemagglutinin (HA) gene genetically related to H5N8 viruses detected in South Korea in 2014 and the neura...

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“…Culture systems of differentiated primary epithelial cells from human and animal airways, especially derived from the trachea, provide valuable in vitro models for characterization of cellular tropism and infectivity of influenza viruses (24)(25)(26)(27)(28)(29)(30)(31). Differentiated tracheal epithelial cell cultures offer numerous advantages, including greater control of experimental conditions and the ability to study epithelial cell function in the absence of other cell types, such as cells representing submucosal glands, all of which can contribute valuable information for in vivo studies.…”

mentioning

confidence: 99%

Tropism and Infectivity of Influenza Virus, Including Highly Pathogenic Avian H5N1 Virus, in Ferret Tracheal Differentiated Primary Epithelial Cell Cultures

Zeng

Goldsmith

Maines

et al. 2013

J Virol

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Tropism and adaptation of influenza viruses to new hosts is partly dependent on the distribution of the sialic acid (SA) receptors to which the viral hemagglutinin (HA) binds. Ferrets have been established as a valuable in vivo model of influenza virus pathogenesis and transmission because of similarities to humans in the distribution of HA receptors and in clinical signs of infection. In this study, we developed a ferret tracheal differentiated primary epithelial cell culture model that consisted of a layered epithelium structure with ciliated and nonciliated cells on its apical surface. We found that human-like (␣2,6-linked) receptors predominated on ciliated cells, whereas avian-like (␣2,3-linked) receptors, which were less abundant, were presented on nonciliated cells. When we compared the tropism and infectivity of three human (H1 and H3) and two avian (H1 and H5) influenza viruses, we observed that the human influenza viruses primarily infected ciliated cells and replicated efficiently, whereas a highly pathogenic avian H5N1 virus (A/Vietnam/1203/2004) replicated efficiently within nonciliated cells despite a low initial infection rate. Furthermore, compared to other influenza viruses tested, VN/1203 virus replicated more efficiently in cells isolated from the lower trachea and at a higher temperature (37°C) compared to a lower temperature (33°C). VN/1203 virus infection also induced higher levels of immune mediator genes and cell death, and virus was recovered from the basolateral side of the cell monolayer. This ferret tracheal differentiated primary epithelial cell culture system provides a valuable in vitro model for studying cellular tropism, infectivity, and the pathogenesis of influenza viruses.

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Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways

Cited by 72 publications

References 52 publications

Trade-offs between and within scales: environmental persistence and within-host fitness of avian influenza viruses

Trade-offs between and within scales: environmental persistence and within-host fitness of avian influenza viruses

Pathogenesis and Transmission of Novel Highly Pathogenic Avian Influenza H5N2 and H5N8 Viruses in Ferrets and Mice

Tropism and Infectivity of Influenza Virus, Including Highly Pathogenic Avian H5N1 Virus, in Ferret Tracheal Differentiated Primary Epithelial Cell Cultures

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