Respiratory transmission of an avian H3N8 influenza virus isolated from a harbour seal

Karlsson, Erik A.; Ip, Hon S.; Hall, Jeffrey S.; Yoon, Sun Woo; Johnson, Jim; Beck, Melinda A.; Webby, Richard J.; Schultz‐Cherry, Stacey

doi:10.1038/ncomms5791

Cited by 61 publications

(61 citation statements)

References 41 publications

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“…Thus, current vaccines against the contemporary seasonal H3N2 viruses circulating appear to be a poor match for the seal11 virus should it ever successfully adapt to humans. The recent publication by Karlsson et al showed that recent seasonal vaccination of humans failed to elicit cross-reactive antibody against the virus, suggesting a lack of population immunity (65).…”

Section: Resultsmentioning

confidence: 99%

“…More recent data using solid-phase glycan binding assays also suggested greater binding affinity for ␣2-6 receptors (65). To assess this observation and to gain further insight into the interactions of this A(H3N8) virus with host receptors, glycan microarray analyses of both seal11 recHA and a virus from the same outbreak, A/harbor seal/New Hampshire/179629/2011, were performed.…”

Section: Resultsmentioning

confidence: 99%

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Structural and Functional Analysis of Surface Proteins from an A(H3N8) Influenza Virus Isolated from New England Harbor Seals

Yang

Nguyen

Carney

et al. 2015

J Virol

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In late 2011, an A(H3N8) influenza virus infection resulted in the deaths IMPORTANCECross-species transmission of zoonotic influenza viruses increases public health concerns. Here, we report a molecular and structural study of the major surface proteins from an A(H3N8) influenza virus isolated from New England harbor seals. The results improve our understanding of these viruses as they evolve and provide important information to aid ongoing risk assessment analyses as these zoonotic influenza viruses continue to circulate and adapt to new hosts. Influenza A viruses (IAVs) are classified into subtypes according to the serological reactivity of their surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA) (1, 2). While 16 HA (H1 to H16) and 9 NA (N1 to N9) subtypes have been identified in wild aquatic birds in the last 100 years, only 3 have adapted to the human population, resulting in four pandemics: H1N1 in 1918 and 2009, H2N2 in 1957, and H3N2 in 1968 (3-6). Although aquatic birds are believed to be the natural reservoir for influenza viruses (7), two novel subtypes of influenza A viruses, H17N10 and H18N11, were recently described in New World bats, which thus may be an alternate reservoir of influenza viruses in nature (8,9).Since the first isolation of H1N1 IAV in swine (10) and the subsequent observation that ferrets were susceptible to IAV (11), it became evident that multiple IAV subtypes of either avian or human descent can infect a number of mammalian species (1). Indeed, over the last decade, the perception and impact of influenza virus infections in animals have changed dramatically as a result of a number of recent outbreaks in poultry involving viruses from the H5, H7, and H9 subtypes that resulted in Ͼ1,000 human infections, as well as the swine origin of the recent A(H1N1)pdm09 pandemic virus (4,(12)(13)(14). This has prompted some governments to invest heavily in global surveillance, research, and capacity building. Public health officials now have a keen interest in all IAVs, but particularly in whether animals, such as pigs, that are closely associated with humans can represent a possible pathway for increased interspecies virus adaptation and transmission.Similar to the infection of pigs, IAV (i.e., H7N7, H4N5, H3N3, H13N2, H13N9, and H4N6 subtypes) and influenza B virus infections have been detected in marine mammals, including seals, whales, and sea otters (15)(16)(17)(18)(19)(20)(21)(22). In November 2011, a marine mammal "unusual mortality event" was declared for Maine, New Hampshire, and northern Massachusetts in response to a large number of deaths in the New England harbor seal population. Sequence analysis revealed that an avian-like H3N8 influenza A virus, A/harbor seal/Massachusetts/1/2011 (seal11), was the cause of the outbreak (23). Although A(H3N8), usually found in avian, canine, equine, and swine hosts (24-27), had been isolated from a seal prior to this event (28), the high mortality observed increased interest from public health officials.Here, we focus our...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Structural and Functional Analysis of Surface Proteins from an A(H3N8) Influenza Virus Isolated from New England Harbor Seals

Yang

Nguyen

Carney

et al. 2015

J Virol

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“…To test whether LPS binds to virions, we used a modified version of a solid-phase influenza receptor binding assay described previously 8 . Briefly, H1N1 PR8 virions, at varying dilutions, were bound to fetuin A (Sigma) coated plates overnight at 4 °C.…”

Section: Bindingmentioning

confidence: 99%

“…All past pandemics of IAV in humans and outbreaks in livestock have origins in viruses that previously circulated among wild aquatic birds, which are the natural reservoir for the virus 8 . In wild birds, the virus transmits primarily via the fecal-oral route 9 .…”

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Bacterial lipopolysaccharide reduces the stability of avian and human influenza viruses

Bandoro

Runstadler

2017

Preprint

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Subtype and host-origin of the viruses were shown to affect the extent to which IAV was susceptible to LPS. Furthermore, using a receptor-binding assay and transmission electron microscopy, we observed that LPS binds to and affects the morphology of influenza virions.Influenza A virus (IAV) is a global threat, infecting 5-10% of adults and 20-30% of children globally every year 5, and infections in humans and highly-pathogenic IAV outbreaks in livestock substantially burden the economy 6,7 . .Commensal bacteria and their products can indirectly protect against IAV infection by interacting with the host's immune system (Fig. 1A). In the absence of commensal bacteria, mice produced impaired type I/II interferon responses, CD4/CD8 T cell responses, and antibody production to All rights reserved. No reuse allowed without permission.was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/146266 doi: bioRxiv preprint first posted online Jun. 5, 2017; 3 IAV infection 3,4 . Moreover, mice pretreated with bacterial lipopolysaccharide (LPS), a product present on the exterior surface and shed by all Gram-negative bacteria, triggered a TLR4 mediated antiviral response to protect the hosts from lethal infection with IAV 12,13 . In contrast, LPS binds directly to the capsid protein of poliovirus, increasing cell attachment and the ability of the virions to remain infectious at increased temperatures 14 , and LPS binding to mouse mammary tumor virus (MMTV) enables increased immune evasion and successful transmission of the virus 15,16 . In the case of influenza, it is unclear whether commensal bacteria and LPS are interacting directly with IAV in addition to their indirect effects on the immune system.We first tested whether GI tract-derived bacteria can affect the stability of IAV. A panel of thirteen heat-killed bacteria derived from the GI microbiome (Table S1), standardized by protein content, and a water control were incubated individually with a human WSN H1N1-GFP virus for 1h at 48 °C. Stability was assessed by measuring the percentage of infected cells (those expressing GFP) by flow cytometry after an overnight infection. Eleven of the thirteen bacterial strains significantly decreased the stability of the virus after incubation compared to the water control (Fig. 1B). Our results indicate the reduction in infectivity was not due to the diluted bacterial products being cytotoxic ( Fig. S1A), nor was the decrease in infectivity due to the presence of bacteria or their products limiting the susceptibility of host-cells to infection (Fig. S1B). This suggests that the observed reduction in thermal stability may be due to the virus interacting directly with the bacterial cells and/or their products.Because there was a wide range in the extent to which bacterial strains reduced viral stability, the specific composition of a host's microbiome could influence its susceptibility to infectio...

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“…This virus contained mutations in the HA gene that are associated with mammalian pathogenicity and that were shown to confer the ability to transmit via respiratory droplets on highly pathogenic avian H5N1 viruses (10)(11)(12). In addition, Karlsson et al have recently shown that the seal/NH/11 virus has increased affinity for ␣2,6-linked sialic acids, replicates in human lung cells, and transmits via respiratory droplets in ferrets (13). 6 PFU of the H3N8 ca vaccine virus in 50 l. Mock-inoculated controls received Leibovitz-15 (L15) medium alone.…”

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confidence: 99%

A Single Dose of an Avian H3N8 Influenza Virus Vaccine Is Highly Immunogenic and Efficacious against a Recently Emerged Seal Influenza Virus in Mice and Ferrets

Baz

Paskel

Matsuoka

et al. 2015

J Virol

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H3N8 influenza viruses are a commonly found subtype in wild birds, usually causing mild or no disease in infected birds. However, they have crossed the species barrier and have been associated with outbreaks in dogs, pigs, donkeys, and seals and therefore pose a threat to humans. A live attenuated, cold-adapted (ca) H3N8 vaccine virus was generated by reverse genetics using the wild-type (wt) hemagglutinin ( We also analyzed human sera against the tl/TX/079/07 H3N8 avian influenza virus and observed low but detectable antibody reactivity in elderly subjects, suggesting that older H3N2 influenza viruses confer some cross-reactive antibody. The latter observation was confirmed in a ferret study. The safety, immunogenicity, and efficacy of the tl/TX/079/07 ca vaccine in mice and ferrets support further evaluation of this vaccine in humans for use in the event of transmission of an H3N8 avian influenza virus to humans. The human and ferret serology data suggest that a single dose of the vaccine may be sufficient in older subjects. IMPORTANCEAlthough natural infection of humans with an avian H3N8 influenza virus has not yet been reported, this influenza virus subtype has already crossed the species barrier and productively infected mammals. Pandemic preparedness is an important public health priority. Therefore, we generated a live attenuated avian H3N8 vaccine candidate and demonstrated that a single dose of the vaccine was highly immunogenic and protected mice and ferrets against homologous and heterologous H3N8 avian viruses. Influenza is an important disease in humans and animals. Influenza A viruses can cross the species barriers intact or following reassortment and have the potential to cause devastating pandemics in humans (1). Pandemic preparedness for influenza has generally been focused on highly pathogenic H5 and H7 avian influenza viruses. However, it is impossible to predict when and where an influenza pandemic will appear, how severe it will be, and which subtype of influenza will emerge as a pandemic strain. Several influenza viruses bearing novel viral gene segments from an animal source have arisen in humans and animals. An example of such an event that underscores the need to consider all influenza virus subtypes was the emergence of the novel H1N1 influenza virus in 2009 despite the ongoing circulation of seasonal H1N1 viruses (2).Avian influenza viruses (AIV) bearing 16 antigenic subtypes of hemagglutinin (HA) and 9 antigenic subtypes of neuraminidase (NA) have been isolated from waterfowl and shorebirds (3, 4), and genetic evidence of H17N10 and H18N11 viruses has been found in bats (5). H3N8 influenza viruses are commonly found in wild birds but are not associated with disease; however, they have been associated with disease outbreaks in dogs (6), horses (7), pigs (8), donkeys (9), and most recently seals (10). Although there have been no known avian H3N8 human cases to date, infections in other mammalian species highlight the ability of this influenza virus subtype to cross the species ...

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Respiratory transmission of an avian H3N8 influenza virus isolated from a harbour seal

Cited by 61 publications

References 41 publications

Structural and Functional Analysis of Surface Proteins from an A(H3N8) Influenza Virus Isolated from New England Harbor Seals

Structural and Functional Analysis of Surface Proteins from an A(H3N8) Influenza Virus Isolated from New England Harbor Seals

Bacterial lipopolysaccharide reduces the stability of avian and human influenza viruses

A Single Dose of an Avian H3N8 Influenza Virus Vaccine Is Highly Immunogenic and Efficacious against a Recently Emerged Seal Influenza Virus in Mice and Ferrets

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