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Literature detail

H19 influenza A virus exhibits species-specific MHC class II receptor usage.

Umut Karakus1,2 Ignacio Mena1,3,4 Jithesh Kottur5 Sara S El Zahed1,6 Rocío Seoane1,6 Soner Yildiz1,6 Leanne Chen7 Magdalena Plancarte8 LeAnn Lindsay8 Rebecca Halpin9 Timothy B Stockwell9 David E Wentworth9 Geert-Jan Boons10,11,12,13 Florian Krammer1,14 Silke Stertz15 Walter Boyce8 Robert P de Vries16 Aneel K Aggarwal5 Adolfo García-Sastre1,3,17,18,19
Affiliations 19 institutions
  1. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
  2. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: [email protected].
  3. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
  4. Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA.
  5. Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  6. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  7. Department of Biology, Barnard College, New York, NY 10027, USA.
  8. Department of Pathology, Microbiology, and Immunology, University of California Davis School of Veterinary Medicine, Davis, CA 95616, USA.
  9. The J. Craig Venter Institute, Rockville, MD 20850, USA.
  10. Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, the Netherlands
  11. Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Rd, Athens, GA 30602, USA
  12. Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CH Utrecht, the Netherlands
  13. Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
  14. Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  15. Institute of Medical Virology, University of Zurich, 8057 Zurich, Switzerland.
  16. Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, the Netherlands.
  17. Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
  18. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
  19. Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: [email protected].
PMID 38889725 2024 Cell Host Microbe eng ppublish
PubMed DOI Browse context

Article

Publication summary

Avian influenza A virus (IAV) surveillance in Northern California, USA, revealed unique IAV hemagglutinin (HA) genome sequences in cloacal swabs from lesser scaups. We found two closely related HA sequences in the same duck species in 2010 and 2013. Phylogenetic analyses suggest that both sequences belong to the recently discovered H19 subtype, which thus far has remained uncharacterized. We demonstrate that H19 does not bind the canonical IAV receptor sialic acid (Sia). Instead, H19 binds to the major histocompatibility complex class II (MHC class II), which facilitates viral entry. Unlike the broad MHC class II specificity of H17 and H18 from bat IAV, H19 exhibits a species-specific MHC class II usage that suggests a limited host range and zoonotic potential. Using cell lines overexpressing MHC class II, we rescued recombinant H19 IAV. We solved the H19 crystal structure and identified residues within the putative Sia receptor binding site (RBS) that impede Sia-dependent entry.

avian influenza virus surveillance entry receptor glycan array HA structure hemagglutinin subtype H19 host range influenza A virus MHC class II receptor binding site recombinant H19 influenza A virus Ducks Hemagglutinin Glycoproteins, Influenza Virus Histocompatibility Antigens Class II Influenza A virus Phylogeny Receptors, Virus Animals Binding Sites

Structured evidence records

Evidence records

4 total
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.70
Key finding

Phylogenetic analysis of avian influenza HA genome sequences from lesser scaups identified a distinct H19 subtype with evolutionary divergence from other known influenza A viruses.

Virus
IAV
Location
Not specified
Supporting text

Avian influenza A virus (IAV) surveillance in Northern California, USA, revealed unique IAV hemagglutinin (HA) genome sequences in cloacal swabs from lesser scaups. We found two closely related HA sequences in the same duck species in 2010 and 2013. Phylogenetic analyses suggest that both sequences belong to the recently discovered H19 subtype, which thus far has remained uncharacterized.

Genes or proteins
hemagglutinin (HA)
Analysis methods
phylogenetic analysis; genome sequencing
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.90
Key finding

H19 influenza A virus adapted to use species-specific MHC class II rather than sialic acid as its entry receptor, altering host range and zoonotic potential.

Virus
IAV
Host
Not specified
Location
Not specified
Supporting text

We demonstrate that H19 does not bind the canonical IAV receptor sialic acid (Sia). Instead, H19 binds to the major histocompatibility complex class II (MHC class II), which facilitates viral entry. Unlike the broad MHC class II specificity of H17 and H18 from bat IAV, H19 exhibits a species-specific MHC class II usage that suggests a limited host range and zoonotic potential.

Genes or proteins
HA
Receptors
MHC class II; sialic acid
Mechanism types
receptor_binding; cell_entry; host_range
Receptor Usage 1 records
Receptor Usage Extraction confidence 1.00
Key finding

H19 influenza A virus binds MHC class II rather than sialic acid for entry, showing species-specific receptor usage compared with H17 and H18 bat influenza viruses.

Virus
IAV
Host
Anas
Location
Not specified
Supporting text

We demonstrate that H19 does not bind the canonical IAV receptor sialic acid (Sia). Instead, H19 binds to the major histocompatibility complex class II (MHC class II), which facilitates viral entry. Unlike the broad MHC class II specificity of H17 and H18 from bat IAV, H19 exhibits a species-specific MHC class II usage that suggests a limited host range and zoonotic potential.

Method
binding assay; structural analysis; cell-entry assay
Receptors
MHC class II
Zoonotic Surveillance 1 records
Zoonotic Surveillance Extraction confidence 0.90
Key finding

Surveillance of avian influenza A viruses in Northern California identified H19 subtype sequences in lesser scaups using cloacal swab samples.

Virus
IAV
Location
United States United States
Supporting text

Avian influenza A virus (IAV) surveillance in Northern California, USA, revealed unique IAV hemagglutinin (HA) genome sequences in cloacal swabs from lesser scaups.

Sample type
cloacal swab
Geographic raw
Northern California, USA
Country inferred
United States