Potential for Low-Pathogenic Avian H7 Influenza A Viruses To Replicate and Cause Disease in a Mammalian Model

ABSTRACT H7 subtype influenza A viruses are widely distributed and have been responsible for human infections and numerous outbreaks in poultry with significant impact. Despite this, the disease-causing potential of the precursor low-pathogenic (LP) H7 viruses from the wild bird reservoir has not been investigated. Our objective was to assess the disease-causing potential of 30 LP H7 viruses isolated from wild avian species in the United States and Canada using the DBA/2J mouse model. Without prior mammalian adaptation, the majority of viruses, 27 (90%), caused mortality in mice. Of these, 17 (56.7%) caused 100% mortality and 24 were of pathogenicity similar to that of A/Anhui/1/2013 (H7N9), which is highly pathogenic in mice. Viruses of duck origin were more pathogenic than those of shorebird origin, as 13 of 18 (72.2%) duck origin viruses caused 100% mortality while 4 of 12 (33.3%) shorebird origin viruses caused 100% mortality, despite there being no difference in mean lung viral titers between the groups. Replication beyond the respiratory tract was also evident, particularly in the heart and brain. Of the 16 viruses studied for fecal shedding, 11 were detected in fecal samples. These viruses exhibited a strong preference for avian-type α2,3-linked sialic acids; however, binding to mammalian-type α2,6-linked sialic acids was also detected. These findings indicate that LP avian H7 influenza A viruses are able to infect and cause disease in mammals without prior adaptation and therefore pose a potential public health risk. IMPORTANCE Low-pathogenic (LP) avian H7 influenza A viruses are widely distributed in the avian reservoir and are the precursors of numerous outbreaks of highly pathogenic avian influenza viruses in commercial poultry farms. However, unlike highly pathogenic H7 viruses, the disease-causing potential of LP H7 viruses from the wild bird reservoir has not been investigated. To address this, we studied 30 LP avian H7 viruses isolated from wild avian species in the United States and Canada using the DBA/2J mouse model. Surprisingly, the majority of these viruses, 90%, caused mortality in mice without prior mammalian adaptation, and 56.7% caused 100% mortality. There was also evidence of spread beyond the respiratory tract and fecal shedding. Therefore, the disease-causing potential of LP avian H7 influenza A viruses in mammals may be underestimated, and these viruses therefore pose a potential public health risk.

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The enigma of the apparent disappearance of Eurasian highly pathogenic H5 clade 2.3.4.4 influenza A viruses in North American waterfowl

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1608853113 ◽

2016 ◽

Vol 113 (32) ◽

pp. 9033-9038 ◽

Cited By ~ 37

Author(s):

Scott Krauss ◽

David E. Stallknecht ◽

Richard D. Slemons ◽

Andrew S. Bowman ◽

Rebecca L. Poulson ◽

...

Keyword(s):

United States ◽

North America ◽

North American ◽

Influenza A ◽

Wild Bird ◽

Animal Health ◽

The United States ◽

Influenza Viruses ◽

Influenza A Viruses ◽

Highly Pathogenic

One of the major unresolved questions in influenza A virus (IAV) ecology is exemplified by the apparent disappearance of highly pathogenic (HP) H5N1, H5N2, and H5N8 (H5Nx) viruses containing the Eurasian hemagglutinin 2.3.4.4 clade from wild bird populations in North America. The introduction of Eurasian lineage HP H5 clade 2.3.4.4 H5N8 IAV and subsequent reassortment with low-pathogenic H?N2 and H?N1 North American wild bird-origin IAVs in late 2014 resulted in widespread HP H5Nx IAV infections and outbreaks in poultry and wild birds across two-thirds of North America starting in November 2014 and continuing through June 2015. Although the stamping out strategies adopted by the poultry industry and animal health authorities in Canada and the United States—which included culling, quarantining, increased biosecurity, and abstention from vaccine use—were successful in eradicating the HP H5Nx viruses from poultry, these activities do not explain the apparent disappearance of these viruses from migratory waterfowl. Here we examine current and historical aquatic bird IAV surveillance and outbreaks of HP H5Nx in poultry in the United States and Canada, providing additional evidence of unresolved mechanisms that restrict the emergence and perpetuation of HP avian influenza viruses in these natural reservoirs.

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Reassortment between Swine H3N2 and 2009 Pandemic H1N1 in the United States Resulted in Influenza A Viruses with Diverse Genetic Constellations with Variable Virulence in Pigs

Journal of Virology ◽

10.1128/jvi.01763-16 ◽

2016 ◽

Vol 91 (4) ◽

Cited By ~ 21

Author(s):

Daniela S. Rajão ◽

Rasna R. Walia ◽

Brian Campbell ◽

Phillip C. Gauger ◽

Alicia Janas-Martindale ◽

...

Keyword(s):

Public Health ◽

United States ◽

Genetic Diversity ◽

Influenza A ◽

The United States ◽

H1n1 Pandemic ◽

Influenza A Viruses ◽

Swine Industry ◽

Viral Shedding ◽

Increased Risk

ABSTRACT Repeated spillovers of the H1N1 pandemic virus (H1N1pdm09) from humans to pigs resulted in substantial evolution of influenza A viruses infecting swine, contributing to the genetic and antigenic diversity of influenza A viruses (IAV) currently circulating in swine. The reassortment with endemic swine viruses and maintenance of some of the H1N1pdm09 internal genes resulted in the circulation of different genomic constellations in pigs. Here, we performed a whole-genome phylogenetic analysis of 368 IAV circulating in swine from 2009 to 2016 in the United States. We identified 44 different genotypes, with the most common genotype (32.33%) containing a clade IV-A HA gene, a 2002-lineage NA gene, an M-pdm09 gene, and remaining gene segments of triple reassortant internal gene (TRIG) origin. To understand how different genetic constellations may relate to viral fitness, we compared the pathogenesis and transmission in pigs of six representative genotypes. Although all six genotypes efficiently infected pigs, they resulted in different degrees of pathology and viral shedding. These results highlight the vast H3N2 genetic diversity circulating in U.S. swine after 2009. This diversity has important implications in the control of this disease by the swine industry, as well as a potential risk for public health if swine-adapted viruses with H1N1pdm09 genes have an increased risk to humans, as occurred in the 2011-2012 and 2016 human variant H3N2v cases associated with exhibition swine. IMPORTANCE People continue to spread the 2009 H1N1 pandemic (H1N1pdm09) IAV to pigs, allowing H1N1pdm09 to reassort with endemic swine IAV. In this study, we determined the 8 gene combinations of swine H3N2 IAV detected from 2009 to 2016. We identified 44 different genotypes of H3N2, the majority of which contained at least one H1N1pdm09 gene segment. We compared six representative genotypes of H3N2 in pigs. All six genotypes efficiently infected pigs, but they resulted in different degrees of lung damage and viral shedding. These results highlight the vast genetic diversity of H3N2 circulating in U.S. swine after 2009, with important implications for the control of IAV for the swine industry. Because H1N1pdm09 is also highly adapted to humans, these swine viruses pose a potential risk to public health if swine-adapted viruses with H1N1pdm09 genes also have an increased risk for human infection.

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Evaluating interest in an influenza A(H5N1) vaccine among laboratory workers who work with highly-pathogenic avian influenza viruses in the United States

Vaccine ◽

10.1016/j.vaccine.2017.10.104 ◽

2018 ◽

Vol 36 (2) ◽

pp. 306-312

Author(s):

Kate E. Russell ◽

J.S. Bresee ◽

J.M. Katz ◽

S.J. Olsen

Keyword(s):

United States ◽

Influenza A ◽

Highly Pathogenic Avian Influenza ◽

The United States ◽

Influenza Viruses ◽

Avian Influenza Viruses ◽

Highly Pathogenic ◽

Pathogenic Avian Influenza ◽

Laboratory Workers ◽

H5n1 Vaccine

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Antigenic evolution of H3N2 influenza A viruses in swine in the United States from 2012 to 2016

Influenza and Other Respiratory Viruses ◽

10.1111/irv.12610 ◽

2018 ◽

Vol 13 (1) ◽

pp. 83-90 ◽

Cited By ~ 9

Author(s):

Marcus J. Bolton ◽

Eugenio J. Abente ◽

Divya Venkatesh ◽

Jered A. Stratton ◽

Michael Zeller ◽

...

Keyword(s):

United States ◽

Influenza A ◽

The United States ◽

Influenza A Viruses ◽

Antigenic Evolution ◽

H3n2 Influenza

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Plague and Pregnancy: Why Special Considerations Are Needed

Clinical Infectious Diseases ◽

10.1093/cid/ciz1232 ◽

2020 ◽

Vol 70 (Supplement_1) ◽

pp. S27-S29

Author(s):

Dana Meaney-Delman ◽

Nadia L Oussayef ◽

Margaret A Honein ◽

Christina A Nelson

Keyword(s):

Public Health ◽

United States ◽

At Risk ◽

Pregnant Women ◽

Yersinia Pestis ◽

The United States ◽

Highly Pathogenic ◽

Pathogenic Organism ◽

Public Health Emergencies ◽

Life Threatening

Abstract Pregnant women are an important at-risk population to consider during public health emergencies. These women, like nonpregnant adults, may be faced with the risk of acquiring life-threatening infections during outbreaks or bioterrorism (BT) events and, in some cases, can experience increased severity of infection and higher morbidity compared with nonpregnant adults. Yersinia pestis, the bacterium that causes plague, is a highly pathogenic organism. There are 4 million births annually in the United States, and thus the unique needs of pregnant women and their infants should be considered in pre-event planning for a plague outbreak or BT event.

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Potential Public Health Effects of Reducing Nicotine Levels in Cigarettes in the United States

New England Journal of Medicine ◽

10.1056/nejmsr1714617 ◽

2018 ◽

Vol 378 (18) ◽

pp. 1725-1733 ◽

Cited By ~ 60

Author(s):

Benjamin J. Apelberg ◽

Shari P. Feirman ◽

Esther Salazar ◽

Catherine G. Corey ◽

Bridget K. Ambrose ◽

...

Keyword(s):

Public Health ◽

United States ◽

Health Effects ◽

The United States ◽

Potential Public Health

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The Emerging Urgency of Mitigating Environmental Impacts and Potential Public Health Risks of the United States Postal Service

Environmental Claims Journal ◽

10.1080/10406026.2018.1442077 ◽

2018 ◽

Vol 30 (2) ◽

pp. 142-150

Author(s):

Robert A. Michaels

Keyword(s):

Public Health ◽

United States ◽

Environmental Impacts ◽

Health Risks ◽

The United States ◽

Postal Service ◽

United States Postal Service ◽

Public Health Risks ◽

Potential Public Health ◽

United States Postal

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Introduction, Evolution, and Dissemination of Influenza A Viruses in Exhibition Swine in the United States during 2009 to 2013

Journal of Virology ◽

10.1128/jvi.01457-16 ◽

2016 ◽

Vol 90 (23) ◽

pp. 10963-10971 ◽

Cited By ~ 11

Author(s):

Martha I. Nelson ◽

Karla M. Stucker ◽

Seth A. Schobel ◽

Nídia S. Trovão ◽

Suman R. Das ◽

...

Keyword(s):

United States ◽

Population Dynamics ◽

Influenza A Virus ◽

Influenza A ◽

The United States ◽

Viral Population ◽

Influenza A Viruses ◽

Swine Industry ◽

Virus Diversity ◽

Agricultural Fairs

ABSTRACT The swine-human interface created at agricultural fairs, along with the generation of and maintenance of influenza A virus diversity in exhibition swine, presents an ongoing threat to public health. Nucleotide sequences of influenza A virus isolates collected from exhibition swine in Ohio ( n = 262) and Indiana ( n = 103) during 2009 to 2013 were used to investigate viral evolution and movement within this niche sector of the swine industry. Phylogenetic and Bayesian analyses were employed to identify introductions of influenza A virus to exhibition swine and study viral population dynamics. In 2013 alone, we identified 10 independent introductions of influenza A virus into Ohio and/or Indiana exhibition swine. Frequently, viruses from the same introduction were identified at multiple fairs within the region, providing evidence of rapid and widespread viral movement within the exhibition swine populations of the two states. While pigs moving from fair to fair to fair is possible in some locations, the concurrent detection of nearly identical strains at several fairs indicates that a common viral source was more likely. Importantly, we detected an association between the high number of human variant H3N2 (H3N2v) virus infections in 2012 and the widespread circulation of influenza A viruses of the same genotype in exhibition swine in Ohio fairs sampled that year. The extent of viral diversity observed in exhibition swine and the rapidity with which it disseminated across long distances indicate that novel strains of influenza A virus will continue to emerge and spread within exhibition swine populations, presenting an ongoing threat to humans. IMPORTANCE Understanding the underlying population dynamics of influenza A viruses in commercial and exhibition swine is central to assessing the risk for human infections with variant viruses, including H3N2v. We used viral genomic sequences from isolates collected from exhibition swine during 2009 to 2013 to understand how the peak of H3N2v cases in 2012 relates to long-term trends in the population dynamics of pandemic viruses recently introduced into commercial and exhibition swine in the United States. The results of our spatial analysis underscore the key role of rapid viral dispersal in spreading multiple genetic lineages throughout a multistate network of agricultural fairs, providing opportunities for divergent lineages to coinfect, reassort, and generate new viral genotypes. The higher genetic diversity of genotypes cocirculating in exhibition swine since 2013 could facilitate the evolution of new reassortants, potentially with even greater ability to cause severe infections in humans or cause human-to-human transmission, highlighting the need for continued vigilance.

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