Determining the Replication Kinetics and Cellular Tropism of Influenza D Virus on Primary Well-Differentiated Human Airway Epithelial Cells.

Melle Holwerda,Laura Laloli,Hanspeter Stalder,Ronald Dijkman,Isabel Stürmer,Jasmine Portmann,Jenna Kelly

doi:10.3390/v11040377

Melle Holwerda, Laura Laloli + Show 5 more

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https://doi.org/10.3390/v11040377

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Journal: Viruses	Publication Date: Apr 24, 2019
Citations: 80	License type: CC BY 4.0

Affiliation: University of Bern

Abstract

Influenza viruses are notorious pathogens that frequently cross the species barrier with often severe consequences for both animal and human health. In 2011, a novel member of the Orthomyxoviridae family, Influenza D virus (IDV), was identified in the respiratory tract of swine. Epidemiological surveys revealed that IDV is distributed worldwide among livestock and that IDV-directed antibodies are detected in humans with occupational exposure to livestock. To identify the transmission capability of IDV to humans, we determined the viral replication kinetics and cell tropism using an in vitro respiratory epithelium model of humans. The inoculation of IDV revealed efficient replication kinetics and apical progeny virus release at different body temperatures. Intriguingly, the replication characteristics of IDV revealed higher replication kinetics compared to Influenza C virus, despite sharing the cell tropism preference for ciliated cells. Collectively, these results might indicate why IDV-directed antibodies are detected among humans with occupational exposure to livestock.

Highlights

After the initial discovery of Influenza D virus (IDV) in 2011, among swine with Influenza-like symptoms, knowledge about this new genus in the family of Orthomyxoviridae is increasing [1,2].Epidemiological studies have shown that the virus has a worldwide distribution, whereby at least two distinct genetic lineages are cocirculating and reassorting [3,4,5,6,7,8,9,10]
We demonstrate that IDV replicates efficiently in an in vitro surrogate model of the in vivo respiratory epithelium at ambient temperatures that correspond to the human upper and lower respiratory tract
We demonstrate that IDV viral progeny is replication competent, as it can be efficiently sequentially propagated onto well-differentiated Human Airway Epithelial Cell (hAEC) cultures from different donors at both 33 ◦ C and 37 ◦ C

Summary

Introduction

After the initial discovery of Influenza D virus (IDV) in 2011, among swine with Influenza-like symptoms, knowledge about this new genus in the family of Orthomyxoviridae is increasing [1,2].Epidemiological studies have shown that the virus has a worldwide distribution, whereby at least two distinct genetic lineages are cocirculating and reassorting [3,4,5,6,7,8,9,10]. After the initial discovery of Influenza D virus (IDV) in 2011, among swine with Influenza-like symptoms, knowledge about this new genus in the family of Orthomyxoviridae is increasing [1,2]. Because of the high seroprevalence, cattle is the proposed natural reservoir of IDV, in which IDV causes mild respiratory disease symptoms [11]. IDV-specific antibodies have been detected in swine, feral swine, equine, ovine, caprine and camelid species, suggesting a broad host tropism for IDV [3,4,9,12,13,14]. The most striking observation is the detection of IDV-directed antibodies among humans with occupational exposure to livestock [15].

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