Shotgun glycomics of pig lung identifies natural endogenous receptors for influenza viruses

Byrd-Leotis, Lauren; Liu, Renpeng; Bradley, Konrad C.; Lasanajak, Yi; Cummings, Sandra F.; Song, Xuezheng; Heimburg-Molinaro, Jamie; Galloway, Summer E.; Culhane, Marie; Smith, David F.; Steinhauer, David A.; Cummings, Richard D.

doi:10.1073/pnas.1323162111

Cited by 99 publications

(136 citation statements)

References 64 publications

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“…There are similarities in the aims of the beam search approach and that of the "shotgun" glycomics of Cummings and colleagues (33)(34)(35)(36). Both are to characterize ligands among glycans from natural sources, using sequence analyses by MS/MS and applying sequence-specific lectins and antibodies.…”

Section: Discussionmentioning

confidence: 99%

O-Glycome Beam Search Arrays for Carbohydrate Ligand Discovery

Gao

Zhang

et al. 2018

Molecular & Cellular Proteomics

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O-glycosylation is a post-translational modification of proteins crucial to molecular mechanisms in health and disease. O-glycans are typically highly heterogeneous. The involvement of specific O-glycan sequences in many bio-recognition systems is yet to be determined because of a lack of efficient methodologies. We describe here a targeted microarray approach: O-glycome beam search that is both robust and efficient for O-glycan ligand-discovery. Substantial simplification of the complex O-glycome profile and facile chromatographic resolution is achieved by arraying O-glycans as branches, monitoring by mass spectrometry, focusing on promising fractions, and on-array immuno-sequencing. This is orders of magnitude more sensitive than traditional methods. We have applied beam search approach to porcine stomach mucin and identified extremely minor components previously undetected within the O-glycome of this mucin that are ligands for the adhesive proteins of two rotaviruses. The approach is applicable to O-glycome recognition studies in a wide range of biological settings to give insights into glycan recognition structures in natural microenvironments. Molecular & Cellular

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Section: Discussionmentioning

confidence: 99%

O-Glycome Beam Search Arrays for Carbohydrate Ligand Discovery

Gao

Zhang

et al. 2018

Molecular & Cellular Proteomics

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“…Unlike most avian influenza viruses, swine-adapted viruses preferentially bind to Sia2-6Gal-terminated ("human-type") receptors (50,(69)(70)(71)(72). It is believed, therefore, that adaptation of the HA of avian viruses to receptors in pigs increases viral zoonotic and pandemic potential.…”

Section: Discussionmentioning

confidence: 99%

H1N1 Swine Influenza Viruses Differ from Avian Precursors by a Higher pH Optimum of Membrane Fusion

Baumann

Kouassi

Foni

et al. 2016

J Virol

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The H1N1 Eurasian avian-like swine (EAsw) influenza viruses originated from an avian H1N1 virus. To characterize potential changes in the membrane fusion activity of the hemagglutinin (HA) during avian-to-swine adaptation of the virus, we studied EAsw viruses isolated in the first years of their circulation in pigs and closely related contemporary H1N1 viruses of wild aquatic birds. Compared to the avian viruses, the swine viruses were less sensitive to neutralization by lysosomotropic agent NH 4 Cl in MDCK cells, had a higher pH optimum of hemolytic activity, and were less stable at acidic pH. Eight amino acid substitutions in the HA were found to separate the EAsw viruses from their putative avian precursor; four substitutions-T49 2 S, N72 2 D, R75 2 K, and S113 2 F-were located in the structural regions of the HA2 subunit known to play a role in acid-induced conformational transition of the HA. We also studied low-pH-induced syncytium formation by cell-expressed HA proteins and found that the HAs of the 1918, 1957, 1968, and 2009 pandemic viruses required a lower pH for fusion induction than did the HA of a representative EAsw virus. Our data show that transmission of an avian H1N1 virus to pigs was accompanied by changes in conformational stability and fusion promotion activity of the HA. We conclude that distinctive host-determined fusion characteristics of the HA may represent a barrier for avian-to-swine and swine-to-human transmission of influenza viruses. IMPORTANCEContinuing cases of human infections with zoonotic influenza viruses highlight the necessity to understand which viral properties contribute to interspecies transmission. Efficient binding of the HA to cellular receptors in a new host species is known to be essential for the transmission. Less is known about required adaptive changes in the membrane fusion activity of the HA. Here we show that adaptation of an avian influenza virus to pigs in Europe in 1980s was accompanied by mutations in the HA, which decreased its conformational stability and increased pH optimum of membrane fusion activity. This finding represents the first formal evidence of alteration of the HA fusion activity/stability during interspecies transmission of influenza viruses under natural settings.

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“…Another factor may be the infectious dose. These studies use a dose of 106 EID 50 , whereas studies by Kida et al . and De Vleeschauwer et al .…”

Section: Discussionmentioning

confidence: 99%

“…Inoculation consisted of physically restraining the pigs in an upright position, then dripping 2 ml of virus (1 × 106 EID 50 /ml in minimal essential media) into the nares and conjunctiva; roughly distributed as 0·75 ml per nostril and 0·25 ml per eye.…”

Section: Methodsmentioning

confidence: 99%

Susceptibility of swine to H5 and H7 low pathogenic avian influenza viruses

Balzli

Lager

Vincent

et al. 2016

Influenza Resp Viruses

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BackgroundThe ability of pigs to become infected with low pathogenic avian influenza (LPAI) viruses and then generate mammalian adaptable influenza A viruses is difficult to determine. Yet, it is an important link to understanding any relationship between LPAI virus ecology and possible epidemics among swine and/or humans.ObjectivesAssess susceptibility of pigs to LPAI viruses found within the United States and their direct contact transmission potential.MethodsPigs were inoculated with one of ten H5 or H7 LPAI viruses selected from seven different bird species to test infectivity, virulence, pathogenesis, and potential to transmit virus to contact pigs through histological, RRT‐PCR and seroconversion data.ResultsAlthough pigs were susceptible to infection with each of the LPAI viruses, no clinical disease was recognized in any pig. During the acute phase of the infection, minor pulmonary lesions were found in some pigs and one or more pigs in each group were RRT‐PCR‐positive in the lower respiratory tract, but no virus was detected in upper respiratory tract (negative nasal swabs). Except for one group, one or more pigs in each LPAI group developed antibody. No LPAI viruses transmitted to contact pigs.Conclusions LPAI strains from various bird populations within the United States are capable of infecting pigs. Although adaptability and transmission of individual strains seem unlikely, the subclinical nature of the infections demonstrates the need to improve sampling and testing methods to more accurately measure incidence of LPAI virus infection in pigs, and their potential role in human‐zoonotic LPAI virus dynamics.

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Shotgun glycomics of pig lung identifies natural endogenous receptors for influenza viruses

Cited by 99 publications

References 64 publications

O-Glycome Beam Search Arrays for Carbohydrate Ligand Discovery

O-Glycome Beam Search Arrays for Carbohydrate Ligand Discovery

H1N1 Swine Influenza Viruses Differ from Avian Precursors by a Higher pH Optimum of Membrane Fusion

Susceptibility of swine to H5 and H7 low pathogenic avian influenza viruses

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