Avian Flu Diary: Trop. Med & Inf. Dis.: Mammalian Pathogenicity and Transmissibility of H1 Swine Variant Influenza

Credit ECDC – 125 years of Pandemic History

#13,900

Up until about a decade ago, it was widely believed that in order to spark an influenza pandemic, we would need to see the emergence of a novel subtype; an HA/NA combination that most of the population had not been exposed to during their lifetime.

After all, influenza pandemics over the past 130 had all involved - not just a new subtype - but more specifically, a new HA gene.

The progression of human influenza pandemics over the past 130 years (including the H1N1 psuedo-pandemic of 1977) is believed to have been H2, H3, H1, H2, H3, H1 (see ECDC graphic above).

Expectations were that the next pandemic would need to come from a non-H1 and non-H3 influenza virus, with many experts eyeing an H5 avian virus from Asia (or possibly the return of an H2 virus) as the most likely candidates.

Instead the 2009 pandemic came from totally out of left field, caused by a triple-reassortant swine origin-H1N1 virus that had been kicking around in North American pigs for more than a decade before finally evolving into an easily transmissible pandemic strain.

Since then, swine origin viruses have received a lot more attention and respect, and swine variant viruses like H1N1v, H1N2v, and H3N2v are considered potential pandemic threats.

Over the past 15 years we've seen more than 460 confirmed human infections with these swine-origin viruses, mostly associated with pig exposure at county and state animal exhibits.

Credit CDC

While most of the reported swine variant infections over the past decade have been mild-to-moderate in severity, some people have required hospitalization, and deaths - while rare - have occurred (see J. Virology: Analysis Of A Swine Variant H1N1 Virus Associated With A Fatal Outcome).

The CDC's general risk assessment of these swine variant (H1N1v, H1N2v, H3N2v) viruses reads:

CDC Assessment
Sporadic infections and even localized outbreaks among people with variant influenza viruses may occur. All influenza viruses have the capacity to change and it’s possible that variant viruses may change such that they infect people easily and spread easily from person-to-person. The Centers for Disease Control and Prevention (CDC) continues to monitor closely for variant influenza virus infections and will report cases of H3N2v and other variant influenza viruses weekly in FluView and on the case count tables on this website

We regularly cover swine and swine variant influenza in this blog, both in North America and around the world. A few studies from 2018 include:

BMC Vet.: Novel Reassortant H1N2 & H3N2 Swine Influenza A Viruses - Chile

J. Virology: Pathogenesis & Transmission of H3N2v Viruses Isolated in the United States, 2011-2016

JVI: Divergent Human Origin influenza Viruses Detected In Australian Swine Populations

The `Other' Novel Flu Threat We'll Be Watching This Summer

Emerg. Infect. & Microbes: Novel Triple-Reassortant influenza Viruses In Pigs, Guangxi, China

All of which sets the table for a lengthy, and quite detailed review of swine-origin H1 variant flu viruses, and their pandemic potential - written by researchers at the CDC's NCIRD - and published this week in Tropical Medicine and Infectious Diseases.

While the consensus is that these swine-variant viruses still require additional adaptation to human physiology in order to spark a pandemic, recent history has shown the ability of swine-origin viruses to evolve and adapt to humans.

Due to its length I've only posted a few excerpts from the Abstract and Conclusions, so follow the link to read the study in its entirety.

Trop. Med. Infect. Dis. 2019, 4(1), 41; doi:10.3390/tropicalmed4010041

Review

Sowing the Seeds of a Pandemic? Mammalian Pathogenicity and Transmissibility of H1 Variant Influenza Viruses from the Swine Reservoir

Joanna A. Pulit-Penaloza * , Jessica A. Belser, Terrence M. Tumpey and Taronna R. Maines
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA

Received: 7 January 2019 / Accepted: 20 February 2019 / Published: 27 February 2019

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.

(SNIP)

7. Conclusions

The confounding unpredictability of influenza A viruses and the occasional spillover of influenza viruses from avian to mammalian species are concerning from a public health standpoint. 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]. In addition, the emergence of the 2009 pandemic virus from pigs further supports that viruses prevalent in swine represent plausible pandemic candidates and underscores the need to closely monitor these viruses.

(SNIP)

It is clear that the human population remains vulnerable to exposure to new, often antigenically different influenza virus strains from the swine reservoir and each human exposure brings a risk of adaptation of these viruses to transmit in humans and possibly cause a pandemic. Features such as the ability to bind to human-like receptors, and capacity for high-titer replication in human cell lines, as well as in the respiratory tract of animal models, were commonly observed with H1v viruses. In addition, the studied North American swine viruses isolated from pigs or humans displayed robust transmissibility between cohoused ferrets [31,53,69,98].

Conversely, in comparison to human seasonal and pandemic influenza virus strains, in most cases, H1v viruses transmitted less efficiently via air (in the absence of direct and indirect contact) and had higher HA activation pH thresholds, indicating a lack of human adaptation.

In addition to infections with H1N1 and H1N2 subtype viruses, swine constitute a major source of zoonotic infections with H3N2 subtype viruses. Similar to the H1v variant viruses discussed here, swine-origin H3N2 viruses isolated from humans were also shown to be capable of mammalian infection and transmissibility in the ferret model [108,109].

As influenza virus pandemics are unpredictable, it is unknown if sporadic human infection with viruses from the swine reservoir indicates an enhanced adaptation of these viruses to humans or rather represents a series of dead-end spillover events.

That said, the 2009 H1N1pdm09 pandemic underscored the rapidity in which a swine-origin influenza virus could spread globally. Continued surveillance and study of viruses from the swine reservoir, both isolated from infected swine and humans, will provide additional insight and understanding into the relative risk these influenza viruses pose to humans. Comparative analysis of new and historical strains will aid in identifying viruses that possess enhanced virulence and adaptations allowing for efficient transmission among humans and ultimately will aid in pandemic preparedness efforts.

(Continue . . . )

We generally see the bulk of human swine-variant infections between June and November, which not surprisingly is the the height of the State and County Fair Season in North America.

To raise general awareness, particularly among young people, last summer the CDC - in conjunction with the USDA and 4H - released an ambitious 60-page graphic novel on swine variant flu and how disease detectives investigate outbreaks.