New England harbor seal H3N8 influenza virus retains avian-like receptor specificity

Hussein, Islam T. M.; Krammer, Florian; Ma, Eric; Estrin, Michael; Viswanathan, Karthik; Stebbins, Nathan W.; Quinlan, Devin Scott; Sasisekharan, Ram; Runstadler, Jonathan A.

doi:10.1038/srep21428

Cited by 35 publications

(10 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to avian H10N4 and H4N2 viruses, seal H10N7 virus bound to mammalian SA receptors but retained binding affinity to avian-type receptors. These results are also in accordance with previous reports, which described dual receptor affinity of avian H3N8 viruses isolated from New England harbor seals in 2011, in which the H3N8 affinity to avian 2,3-SA receptors was significantly higher than binding to 2,6-SA receptors [ 36 , 42 , 43 , 44 ]. Increased binding affinity to 2,6-SA receptors may be attributed to the Q220L mutation.…”

Section: Discussionsupporting

confidence: 93%

Impact of Mutations in the Hemagglutinin of H10N7 Viruses Isolated from Seals on Virus Replication in Avian and Human Cells

Dittrich

Scheibner

Salaheldin

et al. 2018

Viruses

View full text Add to dashboard Cite

Wild birds are the reservoir for low-pathogenic avian influenza viruses, which are frequently transmitted to domestic birds and occasionally to mammals. In 2014, an H10N7 virus caused severe mortality in harbor seals in northeastern Europe. Although the hemagglutinin (HA) of this virus was closely related to H10 of avian H10N4 virus, it possessed unique nonsynonymous mutations, particularly in the HA1 subunit in or adjacent to the receptor binding domain and proteolytic cleavage site. Here, the impact of these mutations on virus replication was studied in vitro. Using reverse genetics, an avian H10N4 virus was cloned, and nine recombinant viruses carrying one of eight unique mutations or the complete HA from the seal virus were rescued. Receptor binding affinity, replication in avian and mammalian cell cultures, cell-to-cell spread, and HA cleavability of these recombinant viruses were studied. Results show that wild-type recombinant H10N4 virus has high affinity to avian-type sialic acid receptors and no affinity to mammalian-type receptors. The H10N7 virus exhibits dual receptor binding affinity. Interestingly, Q220L (H10 numbering) in the rim of the receptor binding pocket increased the affinity of the H10N4 virus to mammal-type receptors and completely abolished the affinity to avian-type receptors. No remarkable differences in cell-to-cell spread or HA cleavability were observed. All viruses, including the wild-type H10N7 virus, replicated at higher levels in chicken cells than in human cells. These results indicate that H10N7 acquired adaptive mutations (e.g., Q220L) to enhance replication in mammals and retained replication efficiency in the original avian host.

show abstract

Section: Discussionsupporting

confidence: 93%

Impact of Mutations in the Hemagglutinin of H10N7 Viruses Isolated from Seals on Virus Replication in Avian and Human Cells

Dittrich

Scheibner

Salaheldin

et al. 2018

Viruses

View full text Add to dashboard Cite

show abstract

“…4B ). However, upon further inspection, this virus descended from viruses circulating in North American waterfowl ( 36 ) and has retained its avian-like receptor specificity ( 37 ). Therefore, it is interesting that this seal H3 also appears to retain avian-like resistance to LPS.…”

Section: Resultsmentioning

confidence: 99%

Bacterial Lipopolysaccharide Destabilizes Influenza Viruses

Bandoro

Runstadler

2017

mSphere

View full text Add to dashboard Cite

Influenza A virus (IAV), transmitted primarily via the fecal-oral route in wild birds, encounters high concentrations of bacteria and their products. Understanding the extent to which bacteria affect the infectivity of IAV will lead to a broader understanding of viral ecology in reservoir hosts and may lead to insights for the development of therapeutics in respiratory infection. Herein we show that bacteria and lipopolysaccharide (LPS) interact with and destabilize influenza virions. Moreover, we show that LPS reduces the long-term persistence and freeze-thaw stability of IAV, which is important information for modeling the movement and emergence of novel strains from animal hosts. Our results, demonstrating that the subtype and host origin of a virus also influence its susceptibility to LPS, raise key questions about the fitness of viruses in reservoir hosts, their potential to transmit to humans, and the importance of bacterial-viral interactions in viral ecology.

show abstract

“…In nine examined tracheal swabs (seal nos. [8][9][10][11][12][13][14][15][16] and in three examined nasal swabs (seal nos. 13-15) a positive signal was detected by the influenza A matrix gene real-time RT-PCR.…”

Section: Naturally Infected Harbor Seals With Seal/h10n7mentioning

confidence: 99%

“…In 2011 there was an outbreak of fatal H3N8 influenza virus infection in harbor seals on the coast of New England, United States. This H3N8 virus is most likely of avian origin and the results of some studies suggest adaption to humans by increased binding affinity for the human-type α2,6-sialic acid receptors [7,8], while others do not [9]. In seals this virus caused interstitial pneumonia, hemorrhagic alveolitis and necrotizing bronchitis.…”

Section: Introductionmentioning

confidence: 99%

Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets

Brand¹,

Wohlsein²,

Herfst³

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7) in harbor seals (Phoca vitulina). This epidemic caused high mortality in seals along the north-west coast of Europe and represented a potential risk for human health. To characterize the spectrum of lesions and to identify the target cells and viral distribution, findings in 16 harbor seals spontaneously infected with Seal/H10N7 are described. The seals had respiratory tract inflammation extending from the nasal cavity to bronchi associated with intralesional virus antigen in respiratory epithelial cells. Virus infection was restricted to the respiratory tract. The fatal outcome of the viral infection in seals was most likely caused by secondary bacterial infections. To investigate the pathogenic potential of H10N7 infection for humans, we inoculated the seal virus intratracheally into six ferrets and performed pathological and virological analyses at 3 and 7 days post inoculation. These experimentally inoculated ferrets displayed mild clinical signs, virus excretion from the pharynx and respiratory tract inflammation extending from bronchi to alveoli that was associated with virus antigen expression exclusively in the respiratory epithelium. Virus was isolated only from the respiratory tract. In conclusion, Seal/H10N7 infection in naturally infected harbor seals and experimentally infected ferrets shows that respiratory epithelial cells are the permissive cells for viral replication. Fatal outcome in seals was caused by secondary bacterial pneumonia similar to that in fatal human cases during influenza pandemics. Productive infection of ferrets indicates that seal/H10N7 may possess a zoonotic potential. This outbreak of LPAI from wild birds to seals demonstrates the risk of such occasions for mammals and thus humans.

show abstract

New England harbor seal H3N8 influenza virus retains avian-like receptor specificity

Cited by 35 publications

References 52 publications

Impact of Mutations in the Hemagglutinin of H10N7 Viruses Isolated from Seals on Virus Replication in Avian and Human Cells

Impact of Mutations in the Hemagglutinin of H10N7 Viruses Isolated from Seals on Virus Replication in Avian and Human Cells

Bacterial Lipopolysaccharide Destabilizes Influenza Viruses

Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets

Contact Info

Product

Resources

About