OmniVira

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].
PMID38889725 DOI10.1016/j.chom.2024.05.018 Year2024 Journal Cell host & microbe Cell Host Microbe Languageeng Statusppublish

Abstract

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.

Supporting text Virus Host Location
avian influenza virus surveillance 1 entry receptor 1 glycan array 3 HA structure 1 hemagglutinin subtype H19 1 host range 29 influenza A virus 227 MHC class II 1 receptor binding site 2 recombinant H19 influenza A virus 1 Ducks 81 Hemagglutinin Glycoproteins, Influenza Virus 180 Histocompatibility Antigens Class II 3 Influenza A virus 186 Phylogeny 805 Receptors, Virus 204 Animals 1948 Binding Sites 89 Cell Line 158 Crystallography, X-Ray 32 Host Specificity 132 Humans 1440 Influenza in Birds 341 N-Acetylneuraminic Acid 25

Evidence records

3 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type Viral Detection
1 records
OVE8137 Viral Detection
Key finding

Unique influenza A virus hemagglutinin genome sequences, belonging to the H19 subtype, were detected in cloacal swabs from lesser scaups in Northern California, USA.

Virus
Influenza A virus
Host
lesser scaup Aythya affinis Natural host
Location
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.

Method
genome sequencing | avian influenza A virus surveillance
Sample type
cloacal swabs
Geographic raw
Northern California, USA
Country inferred
USA
Functional Mechanism
1 records · 1 evidence types
Evidence type Receptor Usage
1 records
OVE8139 Receptor Usage
Key finding

H19 influenza A virus uses major histocompatibility complex class II (MHC class II) as its entry receptor instead of the canonical sialic acid receptor.

Virus
Influenza A virus
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.

Method
binding assay | viral entry assay
Receptors
major histocompatibility complex class II | sialic acid
Genomic Evolution
1 records · 1 evidence types
Evidence type Phylogenetic Evolution
1 records
OVE8138 Phylogenetic Evolution
Key finding

Phylogenetic analysis placed the HA sequences detected in lesser scaups within the recently discovered H19 subtype of influenza A virus.

Virus
Influenza A virus
Host
lesser scaup Aythya affinis Natural host
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. Phylogenetic analyses suggest that both sequences belong to the recently discovered H19 subtype, which thus far has remained uncharacterized.

Genes or proteins
HA
Analysis methods
phylogenetic analysis