Abstract
Emergence of genetically and antigenically diverse strains of influenza to which the human population has no or limited immunity necessitates continuous risk assessments to determine the likelihood of these viruses acquiring adaptations that facilitate sustained human-to-human transmission. As the North American swine H1 virus population has diversified over the last century by means of both antigenic drift and shift, in vivo assessments to study multifactorial traits like mammalian pathogenicity and transmissibility of these emerging influenza viruses are critical. In this review, we examine genetic, molecular, and pathogenicity and transmissibility data from a panel of contemporary North American H1 subtype swine-origin viruses isolated from humans, as compared to H1N1 seasonal and pandemic viruses, including the reconstructed 1918 virus. We present side-by-side analyses of experiments performed in the mouse and ferret models using consistent experimental protocols to facilitate enhanced interpretation of in vivo data. Contextualizing these analyses in a broader context permits a greater appreciation of the role that in vivo risk assessment experiments play in pandemic preparedness. Collectively, we find that despite strain-specific heterogeneity among swine-origin H1 viruses, contemporary swine viruses isolated from humans possess many attributes shared by prior pandemic strains, warranting heightened surveillance and evaluation of these zoonotic viruses.
Highlights
Influenza A virus is an enveloped, negative-sense RNA virus containing a segmented genome comprising eight gene segments [1]
These results are in contrast to those reported for the pre-2009 pandemic H1 human seasonal viruses, but are consistent with data observed for North American and Eurasian swine viruses, which, in general, replicated efficiently throughout the respiratory tract of ferrets, infrequently resulting in severe disease and fatal outcomes [69,85]
Swine-origin influenza viruses that cross the species barrier and cause human infections pose a considerable health threat due to their distinct antigenicity, ability to cause mammalian disease, and capacity for enhanced transmission in mammals, which are all virological attributes of pandemic influenza strains [27,31,53,103]
Summary
Influenza A virus is an enveloped, negative-sense RNA virus containing a segmented genome comprising eight gene segments [1]. Several risk assessment tools have been established to improve pandemic preparedness efforts, notably the Influenza Risk Assessment Tool (IRAT) [11] and Tool for Influenza Pandemic Risk Assessment (TIPRA) [12] These rubrics consider properties of the virus, host, and ecological factors; some of the properties in these assessments, especially multifactorial traits such as pathogenicity and transmissibility, are informed by data generated in laboratory mammalian models. According to the CDC, since 2010, H1 subtype viruses from the North American swine reservoir have resulted in 34 human cases with 1 fatality [15] To better contextualize these novel viruses that pose a threat to human health, we performed a comparative analysis of human seasonal and pandemic H1N1 and swine-origin H1N1v and H1N2v influenza viruses, spanning from the reconstructed 1918 pandemic strain to contemporary viruses causing human infections today. As the tremendous genetic heterogeneity among North American H1 swine influenza viruses makes it difficult to contextualize novel influenza strains with previously studied H1 subtype viruses, this review provides an avenue to study dynamic properties in a setting that is as controlled as possible
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