OmniVira

Marked neurotropism and potential adaptation of H5N1 clade 2.3.4.4.b virus in naturally infected domestic cats.

Shubhada K Chothe1,2 Surabhi Srinivas1,2 Sougat Misra1,2 Noel Chandan Nallipogu1,2 Elizabeth Gilbride1,2 Lindsey LaBella1,2 Swastidipa Mukherjee1,2 Christian H Gauthier3 Heidi L Pecoraro4 Brett T Webb4 James M Pipas3 Santhamani Ramasamy1,2 Suresh V Kuchipudi1,2
Affiliations 4 institutions
  1. Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
  2. Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.
  3. Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
  4. Veterinary Diagnostic Laboratory, North Dakota State University, Fargo, ND, USA.
PMID39648950 DOI10.1080/22221751.2024.2440498 Year2025 Journal Emerging microbes & infections Emerg Microbes Infect Languageeng Statusppublish

Abstract

In April 2024, ten cats died in a rural South Dakota (SD) residence, showing respiratory and neurological symptoms. Necropsy and laboratory testing of two cats confirmed H5N1 clade 2.3.4.4b infection. The viral genome sequences are closely related to recent SD cattle H5N1 sequences. Cat H5N1 genomes had unique mutations, including T143A in haemagglutinin, known to affect infectivity and immune evasion, and two novel mutations in PA protein (F314L, L342Q) that may affect polymerase activity and virulence, suggesting potential virus adaptation. Dead cats showed systemic infection with lesions and viral antigens in multiple organs. Higher viral RNA and antigen in the brain indicated pronounced neurotropism. Lectin-histochemistry revealed widespread co-expression of sialic acid α-2,6 and α-2,3 receptors, suggesting cats could serve as mixing vessels for reassortment of avian and mammalian influenza viruses. No differences in clade 2.2 or 2.3.4.4b H5 pseudoviruses binding to cat lung/brain tissues indicated the neurotropism is unlikely mediated by receptor binding affinity.

Supporting text Virus Host Location
A(H5N1) 3 avian influenza 57 cat 22 clade 2.3.4.4b 19 influenza A virus evolution 1 Influenza A viruses 6 neurotropism 2 Cat Diseases 67 Influenza A Virus, H5N1 Subtype 300 Orthomyxoviridae Infections 228 Viral Tropism 45 Animals 1948 Brain 13 Cats 120 Genome, Viral 317 Hemagglutinin Glycoproteins, Influenza Virus 180 Mutation 209 Phylogeny 805 RNA, Viral 193 Virulence 108

Evidence records

4 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type Viral Detection
1 records
OVE8664 Viral Detection
Key finding

H5N1 clade 2.3.4.4b viral infection was confirmed in two domestic cats from South Dakota through necropsy and laboratory testing.

Virus
Influenza A virus H5N1
Host
domestic cat Felis catus Natural host
Location
United States
Supporting text

In April 2024, ten cats died in a rural South Dakota (SD) residence, showing respiratory and neurological symptoms. Necropsy and laboratory testing of two cats confirmed H5N1 clade 2.3.4.4b infection.

Method
necropsy | laboratory testing
Sample type
necropsy tissues
Geographic raw
South Dakota
Country inferred
USA
Functional Mechanism
2 records · 1 evidence types
Evidence type Receptor Usage
2 records
OVE8668 Receptor Usage
Key finding

Lectin-histochemistry showed domestic cats co-express sialic acid α-2,6 and α-2,3 receptors, indicating potential compatibility with both avian and mammalian influenza virus entry.

Virus
Influenza A virus H5N1
Host
domestic cat Felis catus Experimental system
Location
Not specified
Supporting text

Lectin-histochemistry revealed widespread co-expression of sialic acid α-2,6 and α-2,3 receptors, suggesting cats could serve as mixing vessels for reassortment of avian and mammalian influenza viruses.

Method
lectin-histochemistry
Receptors
sialic acid α-2,6 receptor | sialic acid α-2,3 receptor
OVE8669 Receptor Usage
Key finding

Binding assays showed clade 2.2 and 2.3.4.4b H5 pseudoviruses had similar binding to cat lung and brain tissues, indicating cat neurotropism is unlikely due to receptor binding differences.

Virus
Influenza A virus H5
Host
domestic cat Felis catus Experimental system
Location
Not specified
Supporting text

No differences in clade 2.2 or 2.3.4.4b H5 pseudoviruses binding to cat lung/brain tissues indicated the neurotropism is unlikely mediated by receptor binding affinity.

Method
receptor binding assay | pseudovirus binding experiments
Receptors
cell surface receptors in cat lung and brain tissues
Genomic Evolution
1 records · 1 evidence types
Evidence type Phylogenetic Evolution
1 records
OVE8665 Phylogenetic Evolution
Key finding

Phylogenetic analysis showed that cat H5N1 clade 2.3.4.4b genomes were closely related to recent South Dakota cattle H5N1 sequences, indicating an evolutionary link between viruses infecting cats and cattle.

Virus
Influenza A virus H5N1
Host
domestic cat Felis catus Natural host domestic cattle Bos taurus Natural host
Location
Not specified
Supporting text

The viral genome sequences are closely related to recent SD cattle H5N1 sequences.

Analysis methods
phylogenetic analysis