ORGANISMS SEARCHES TOOLS & SERVICES WORKSPACES HELP ABOUT
Uploads 0 0 0%
Jobs

Outbreak

Influenza A virus subtype H5N1, commonly known as avian influenza virus (AIV) or bird flu, has garnered significant attention due to its potential to cause severe illness in both birds and humans. Originating primarily in wild birds, H5N1 can infect domestic poultry, posing significant economic and public health concerns. H5N1 infections are rare in humans but have been associated with high mortality rates, making it a focus of pandemic preparedness efforts. Continuous surveillance and research are crucial for monitoring H5N1 activity, understanding its transmission dynamics, and developing effective control measures to mitigate the risk of widespread outbreaks.

Currently reported and sequenced hosts infected with H5N1.

Isolated outbreaks of H5N1 AIV have been documented since 1996-1997. These outbreaks have revealed ongoing evolution of the H5N1 subtype, in association with an increasingly diverse host range. The current outbreak was first documented in 2020, and spread mainly through migrating birds across Africa, Asia, and Europe, causing significant wild bird deaths and poultry outbreaks. These viruses reached North America by late 2021 and South America in 2022. In late 2022, viruses from this lineage caused an outbreak in a mink farm in Spain, an example of evolving mammalian adaption.

Human infections of AIV H5N1 viruses are tracked by CDC and WHO. Globally, 26 human cases have been documented from Jan 2022-April 2024. More information about these human cases can be seen in a technical report from the CDC. The cases involve H5N1 “clades” (subspecies) 2.3.2.1c and 2.3.4.4b. Most human cases had contact with dead or sick poultry. There has been no reported human-to-human transmission from this period. Since 2020, six human cases of A(H5N1) linked to the 2.3.4.4b clade have been reported to WHO.

In late March 2024, a dairy farm worker experienced redness and discomfort in the right eye. Upon examination, subconjunctival hemorrhage and serious drainage were observed. The worker had close contact with dairy cows, some exhibiting signs of illness consistent with A(H5N1) virus infection. Testing of the farm worker revealed influenza A(H5) clade 2.3.4.4b virus in conjunctival and nasopharyngeal swab specimens. The worker was isolated at home and treated with oseltamivir; the symptoms resolved The virus showed genetic similarity to strains found in Texas dairy cattle and wild birds. Although it maintained avian characteristics, it had a mutation associated with adaptation to mammalian hosts. No genetic markers for antiviral drug resistance were found. The virus's hemagglutinin closely resembled existing candidate vaccine viruses for A(H5N1).

Further testing confirmed HPAI A(H5N1) virus infection. The virus showed genetic similarity to strains found in Texas dairy cattle and wild birds. Although it maintained avian characteristics, it had a mutation associated with adaptation to mammalian hosts. No genetic markers for antiviral drug resistance were found. The virus's hemagglutinin closely resembled existing candidate vaccine viruses for A(H5N1).

Outbreak Awareness Report

Agency Title Description
BV-BRC 2024 Influenza A Virus HPAI H5N1 Outbreak Weekly Report H5N1 Outbreak Weekly Report
CDC H5N1 Bird Flu: Current Situation Summary US-based human case tracking
USDA HPAI Detections in Livestock US-based livestock HPAI analysis
WHO Avian Influenza A(H5N1) - USA Human case report and epidemiology

H5N1 Outbreak Map

The BV-BRC's outbreak response for H5N1 includes a thorough review of the latest updates from the CDC and state websites, including public health and government pages. This ensures timely and accurate information on H5N1 cases in cattle and humans. The provided map represents this collected data, offering a quick overview of the outbreak's impact and serving as an up-to-date representation of detected cases. At times, this will be before genomic information is released, giving BV-BRC users up-to-date information regarding cases that have been detected.

Influenza A Virus

Influenza A virus, a member of the Orthomyxoviridae family, is a significant etiological agent of influenza, an acute respiratory illness with substantial global impact. Characterized by its enveloped structure housing a segmented, negative-sense single-stranded RNA genome, this virus exhibits remarkable genetic plasticity, facilitating rapid evolutionary adaptation and strain diversification.

Preventative strategies against influenza A entail vaccination campaigns targeting prevalent strains alongside infection control measures emphasizing respiratory hygiene and social distancing. Therapeutic interventions, predominantly relying on neuraminidase inhibitors and adamantanes, aim to facilitate symptomatology and mitigate disease progression, particularly when administered promptly following symptom onset.

Influenza A is organized into distinct evolutionary lineages, “clades”, characterized by genetic divergence and phylogenetic clustering. These clades arise from the continuous genetic reassortment and mutation inherent to the virus, leading to novel strains with unique antigenic profiles. Scientists classify influenza A viruses into clades to track their evolutionary trajectories, assess antigenic variation, and select vaccine strains. Understanding the dynamics of influenza A clades is paramount for predicting seasonal epidemics, anticipating pandemics, and developing targeted interventions to mitigate the impact of this ever-evolving viral pathogen on global public health.

Influenza A Genomic Structure: Segmented ssRNA(-) linear genome, encapsidated by nucleoprotein (NP). Contains 8 segments coding for a total of 12-14 proteins depending on strains. Segment sizes range from 890 to 2,341nt. Genome total size is 13.5Kb. See the interactive version at Viral Zone.

Influenza A Taxonomy

  • Realm: Riboviria
  • Kingdom: Orthornavirae
  • Phylum: Negarnaviricota
  • Subphylum: Polyploviricotina
  • Class: Insthoviricetes
  • Order: Articulavirales
  • Family: Orthomyxoviridae
  • Genus: Alphainfluenzavirus
  • Species: Alphainfluenzavirus influenzae
  • Sub-species (of the current 2024 H5N1 outbreak): H5N1, 2.3.4.4b

H-N Decoded

Influenza A viruses are classified into subtypes based on their surface proteins: hemagglutinin (H) and neuraminidase (N) - for example, H5N1, H3N2, etc.

Disease Information

In humans, the influenza A virus spreads efficiently via respiratory droplets, efficiently exploiting host respiratory epithelial cells as its primary replication site. The virus's capacity for antigenic drift and shift is critical to its pathogenic prowess, which evades host immune surveillance, precipitating periodic epidemics and potential pandemics.

Clinical manifestations of influenza A infection encompass a spectrum of symptoms, including fever, malaise, myalgia, respiratory distress, and complications such as pneumonia. The severity of the disease often correlates with host factors, including age, immune status, and underlying health conditions.

Epidemiology

Influenza is a well-studied virus, and much previous work has been done to understand and monitor mutations that may affect virus transmissibility, virulence, and antigenic properties, which could impact vaccine efficacy.

Influenza A viruses are of particular concern due to their ability to infect many hosts, including humans, birds, pigs, and other mammals. The transmission dynamics of influenza A viruses between animals and humans vary depending on the specific virus subtype and the characteristics of the host species involved.

Avian influenza A viruses, such as HPAI A(H5N1), primarily circulate among birds, particularly wild aquatic birds, which serve as natural reservoirs. Transmission to humans typically occurs through direct or close contact with infected poultry or contaminated environments, such as live bird markets or farms. Human infections with avian influenza viruses often result from exposure to respiratory secretions or feces of infected birds. While human-to-human transmission of avian influenza viruses is possible, it usually occurs sporadically and is limited in scope.

In contrast, swine influenza A viruses, such as H1N1 and H3N2, can infect pigs and humans. Transmission of swine influenza viruses from pigs to humans can occur through direct contact with infected pigs, inhalation of virus-containing aerosols, or contact with contaminated surfaces. Certain occupational groups, such as pig farmers and veterinarians, are at higher risk of swine influenza virus exposure.

Influenza A viruses' potential to undergo genetic reassortment in intermediate hosts, such as pigs, poses a risk for the emergence of novel virus strains with pandemic potential. Reassortment occurs when two different influenza viruses infect the same host cell and exchange genetic material, generating a new virus with a combination of genes from both parent viruses.

Effective surveillance and control measures, including monitoring animal populations, early detection of novel virus strains, and implementation of biosecurity measures, are crucial for mitigating the risk of zoonotic transmission of influenza A viruses and reducing the likelihood of pandemic emergence. Additionally, research into the genetic and ecological factors influencing virus transmission between animals and humans is essential for improving our understanding of influenza epidemiology and informing public health interventions.


News

Recent PubMed Articles

    This map provides a comprehensive summary of sequence isolates related to the 2024 H5N1 outbreak. It includes publicly available genomic data counts at both state and country levels. Each marker on the map is interactive, allowing users to click and reveal a detailed breakdown of hosts. Additionally, users can click further to access the corresponding genomic data.

    Loading Map of Seq. Isolates...
    Cases in humans and other hosts (# of human cases / # of other hosts' cases)
    Cases in non-human hosts
    Country-level cases
    State-level cases

    H5N1 Outbreak Genomes

    All H5N1 genomes from 2024 and 2025

    H5N1 Outbreak genomes from GenBank

    H5N1 genomes from 2024 and 2025 that have GenBank accession numbers.

    H5N1 Outbreak genomes assembled from SRA

    H5N1 genomes from 2024 and 2025 in North America assembled from the NCBI Short Read Archive (SRA) database. The BV-BRC assembled and annotated these genomes from SRA records that are not yet linked to a GenBank record.

    Sequence Feature Variant Type (SFVT)

    Search for Sequence Feature Variant Type data

    H5N1 outbreak FASTA, MSA and phylogenetic tree files from 2024 and 2025 available from the BV-BRC FTP Site .

    These files contain the data used to generate the phylogenetic trees provided on the Phylogenetics tab on the H5N1 Outbreak page.

    The data is cleaned following a number of steps. For sequences prior to 2024, H5N1 DNA sequences for segments were downloaded from BV-BRC only from isolates for which all 8 segments were present in the database. This was followed by quality control (QC) and representative sequence selection:

    • For Segment 4, a minimum length cutoff of 1600nt was used, allowing no more than 0.1% undetermined residues (“N”).
    • Representative sequence selection was performed by clustering using cd-hit with a cutoff of 0.98%.
    • Other segments were retained only for those isolates for which Segment 4 passed the QC and clustering step.
    • Sequences prior to 2003 were excluded from the analysis to prevent the resulting trees from being overly long.

    For 2024 sequences, all H5N1 sequences from BV-BRC were used without additional quality control or clustering. While all sequences undergo quality control, users are encouraged to review alignments manually before submitting them to programs specific to ancestral alignment to ensure data accuracy and reliability.

    H5N1 USDA Outbreak BioProject

    The intent of this BioProject is to rapidly share sequences to ensure public transparency and represent affected cattle herds, poultry premises, peridomestic animals, and wild animals that support the phylogeny. Due to the urgency of sequence sharing, epidemiological investigations may still be ongoing; thus, sequences are initially made publicly available with limited metadata.

    H5N1 outbreak raw reads on NCBI SRA .

    The NCBI Sequence Read Archive (SRA) is a public repository maintained by the National Center for Biotechnology Information (NCBI) that stores raw sequencing data. This link provides all SRA records with H5N1 keyword search with data published since 2024.

    H5N1 outbreak data at NCBI Virus Data .

    NCBI Virus is a specialized resource within the National Center for Biotechnology Information (NCBI) that focuses on providing comprehensive access to viral sequence data and related information. This particular link dedicated to H5N1 data since 2024.


    BV-BRC H5N1 Webinar

    Given the current situation surrounding increased cases of H5N1, and transmission in new hosts, the BV-BRC team updated the community on how to find data and submit data and tools to support analysis on the BV-BRC.

    Resource Description
    BV-BRC Annotation Tool Annotation of genomic features using VIGOR4.
    BV-BRC Gene Tree Build your own gene/protein tree using our phylogenetic tree tool.
    BV-BRC Meta-CATS Look for statistically significant position changes using the Metadata-driven comparative analysis tool.
    BV-BRC MSA Tool Choose an alignment algorithm to align sequences.
    BV-BRC Sequence Submission Validate and submit virus sequences to NCBI Genbank.
    BV-BRC Subspecies Classification Assign the genotype/subtype of a virus, based on the genotype/subtype assignments maintained by ICTV.
    BV-BRC Viral Genome Tree Build your own genomic phylogenetic tree using our phylogenetic tree tool.

    Other Resources

    Resource Description
    Advances in Detection Techniques for the H5N1 Avian Influenza Virus Influenza Methods Paper ECDC Avian Influenza Toolkit
    University of Minnesota DashFLUboard - Avian Influenza Tracker Open-source dashboard that offers near real-time tracking and analysis of avian influenza outbreaks.
    Novel Influenza A Virus Infections CDC - Novel Influenza A Virus Infections
    Highly Pathogenic Avian Influenza (HPAI) Detections in Livestock USDA - US-based livestock news and information
    Avian and other zoonotic infection reports WHO - World overview of avian and zoonotic influenza
    HPAI Detection in Wild Bird USDA - Tracking information about wild birds with map and csv file
    Detections of Highly Pathogenic Avian Influenza in Mammals USDA - Tracking information about species which are susceptible to HPAI in US with map and csv file
     
    Last updated on 05/15/2024

    Below are some of useful command line tool reference and examples to search and download bulk data from BV-BRC. Complete command line interface (CLI) guide is available at Command Line Interface. CLI installation guide is available at Installing the BV-BRC Command Line Interface.

    Search Genome

    User can search genomes using p3-all-genomes command. Complete help and guide are at p3-all-genomes.

    Example of p3-all-genomes command.

    Following command is to download segment 4 of h_type 5 for any genomes loaded after 2024-04-01T00:00:00.000Z. Please make sure you format the date correctly.

    $ p3-all-genomes --eq segment,4 --eq h_type,5 --gt date_inserted,"2024-04-01T00:00:00.000Z"
    genome.genome_id
    11320.548370
    11320.548378
    11320.548382
    11320.548394
    11320.548401

    Following commands will get the genome id of all genomes from 2024 from USA with subtype H5N1 in FASTA format.

    $ p3-all-genomes \
      --eq="genome_name,Influenza A virus" \
      --eq=isolation_country,USA \
      --eq=host_common_name,* \
      --eq=collection_year,2024 \
      --eq=subtype,H5N1 \
      | head -n 10 > Influenza_A_virus.txt
    
    #Example output
    $ more Influenza_A_virus.txt
    genome.genome_id
    11320.545895
    11320.545891
    11320.545932
    

    Download Annotation

    User can download annotation in two steps.

    1. Download the GenomeType
    2. Convert the GenomeType to one of following format.
    GenomeType conversion format options
    genbank         Genbank format
    genbank_merged  Genbank format as single merged locus.
    feature_data    Tabular form of feature data
    protein_fasta   Protein translations in fasta format
    contig_fasta    Contig DNA in fasta format
    feature_dna     Feature DNA sequences in fasta format
    gff             GFF format
    embl            EMBL format
    
    More details of commands available at p3-gto and RASTtk, The Incremental Commands.

    1. Download the GenomeType

    First, download the GenomeType using the Genome ID.

    p3-gto [Genome ID]

    Example:

    p3-gto 11320.560905

    2. Convert GenomeType to Desired Format

    Once you have the GenomeType file, you can convert it to your desired format.

    rast-export-genome [Format] < [GenomeType File] > [Output File]
    • Replace [Format] with one of the conversion options (e.g. gff, genbank, protein_fasta, etc.).
    • Replace [GenomeType File] with the filename of the downloaded GenomeType file.
    • Replace [Output File] with the desired name for the converted file.

    Example:

    rast-export-genome gff < 11320.560905.gto > 11320.560905.gto.gff

    Download genome data in FASTA format

    $ p3-genome-fasta -h
    p3-genome-fasta.pl [-h] [long options...] genomeid
    --protein  feature protein fasta
    --feature  feature dna fasta
    --contig   contig dna fasta
    -h --help  display usage information
    

    Example of downloading genome using genome id:

    $ p3-genome-fasta --contig 11320.435309
    >11320.435309.con.0001 segment
    atgagtcttctaaccgaggtcgaaacgtacgttctttctatcattccgtcaggccccctc
    aaagccgagatcgcacagagactggaaagtgtctttgcaggaaagaacacagatcttgag
    …
    

    Example of searching and downloading data using pipe command:

    p3-all-genomes  --eq segment,4 --eq h_type,5 --gt date_inserted,"2024-05-01T00:00:00.000Z" \
     | sed -n '2,$p' | xargs -n 1 p3-genome-fasta --contig

    Search genome list and then download data based on genome list:

    #Search the genome list
    $ p3-all-genomes  --eq segment,4 --eq h_type,5 --gt date_inserted,"2024-05-01T00:00:00.000Z" \
     > genome_list.txt
    
    #Download fasta file for genome list. You can remove the genomes for genome-list as needed
    $ for i in $(cat genome_list.txt); do
        if [ $i != "genome.genome_id" ]; then
           p3-genome-fasta --contig $i
        fi
     done >> genome.fasta
    
    #View the genome fasta file
    $ more genome.fasta
    >388108.3.con.0001
    agcaaaagcaggagttcaaaatgaatccaaatcagaagataataaccatcggatcaatct
    gtatggtaattggaatagttagcttaatgttacaaattgggaacatgatctcaatatggg
    tcagtcattcaattcagacagggaatcaacgccaagctgaaccaatcagcaatactaaat
    ttcttactgagaaagctgtggcttcagtaacattagcgggcaattcatctctttgcccca
    ...act

    Search and download genomes from 2024 from USA with subtype H5N1 in custom FASTA header format.

    $ p3-all-genomes \
        --eq="genome_name,Influenza A virus" \
        --eq=isolation_country,USA \
        --eq=host_common_name,* \
        --eq=collection_year,2024 \
        --eq=subtype,H5N1 \
      | p3-get-genome-contigs \
        --attr=genome_id,accession,description,sequence \
      | p3-tbl-to-fasta \
        --comment=4 3 5 \
      > Influenza_A_virus.ffn
    
    #Example output
    $ more Influenza_A_virus.ffn
    >PP576945 Influenza A virus (A/hooded merganser/South Carolina/W24-028/2024(H5N1)) segment 8 nuclear export protein (NEP)
    and nonstructural protein 1 (NS1) genes, complete cds.
    atggattccaacactgtgtcaagctttcaggtagactgctttctttggcatgtccgcaaa
    cgatttgcagaccaagaactgggtgatgccccattccttgaccggcttcgccgagagcag
    

    Search and download NA gene sequences in FASTA format.

    $ p3-all-genomes \
        --eq="genome_name,Influenza A virus" \
        --eq=isolation_country,USA \
        --eq=host_common_name,* \
        --eq=collection_year,2024 \
        --eq=subtype,H5N1 \
        --eq=segment,6 \
      | p3-get-genome-features \
        --eq=annotation,PATRIC \
        --in=feature_type,CDS,mat_peptide \
        --eq gene,NA \
        --selective \
        --attr=patric_id \
      | p3-get-feature-sequence \
        --dna \
        --col=2 \
      > Influenza_A_virus.fna
    
    #Example output
    $ more Influenza_A_virus.fna
    >fig|11320.570985.CDS.1 neuraminidase
    ATGAATCCAAATCAAAAGATAACAACCATTGGATCAATCTGTATGGTAATTGGGATAGTCAGCTTGATGCTGCAAATTGGGAACATAATCTCAATATGGGTTAGCCATTCAATCCAAA
    CAGGGAATCAATACCAGCCTGAACCATGCAATCAAAGCATCATTACCTATGAGAACAACACCTGGGTAAATCAGACGTATGTCAACATCAGCAATACCAATTTTCTTGCTGAGCAGGC
    TGTTACTTCGGTAACATTAGCGGGCAATTCATCTCTTTGCCCTATTAGTGGGTGGGCAATATACAGTAAGGACAACGGTATAAGAATTGGGTCTAAGGGGGATGTGTTTGTTATAAGA
    GAACCATTCATCTCATGCTCCCACTTGGAATGCAGAACCTTTTTCCTGACCCAGGGAGCTCTGCTGAATGACAAACATTCTAATGGGACAGTTAAAGATAGAAGCCCTTATAGAACTT
    TGATGAGTTGTCCCGTGGGTGAGGCTCCTTCCCCGTACAATTCAAGATTTGAGTCTGTTGCTTGGTCGGCAAGTGCTTGTCATGATGGCATCA
    

    Search and download NA protein from all genomes from 2024 from USA with subtype H5N1 in FASTA format.

    $ p3-all-genomes \
        --eq="genome_name,Influenza A virus" \
        --eq=isolation_country,USA \
        --eq=host_common_name,* \
        --eq=collection_year,2024 \
        --eq=subtype,H5N1 \
        --eq=segment,6 \
      | p3-get-genome-features \
        --eq=annotation,PATRIC \
        --in=feature_type,CDS,mat_peptide \
        --eq gene,NA \
        --selective \
        --attr=patric_id \
      | p3-get-feature-sequence \
        --protein \
        --col=2 \
      > Influenza_A_virus.faa
    
    #Example output
    $ more Influenza_A_virus.faa
    >fig|11320.571776.CDS.1 neuraminidase
    MNPNQKITTIGSICMVIGIVSLMLQIGNIISIWVSHSIQTGNQYQPEPCNQSIITYENNTWVNQTYINISSTNFLAEQAVTSVTLAGNSSLCPISGWAIYSKDNGIRIGSKGDVFVIR
    EPFISCSHLECRTFFLTQGALLNDKHSNGTVKDRSPYRTLMSCPVGEAPSPYNSRFESVAWSASACHDGISWLTIGISGPDNGAVAVLKYNGIITDTIKSWRNNILRTQESECACVNG
    SCFTVMTDGPSNGQASYKIFKIEKGKVVKSVEMNAPNYHYEECSCYPDAGDIMCVCRDNWHGSNRPWVSFNQNLEYQIGYICSGIFGDNPRPNDGTGSCSPMPSNGAYGVKGFSFKYG
    NGVWIGRTKSTSSRSGFEMIWDPNGWTETDSSFSVKQDIVEITDWSGYSGSFVQHPELTGLDCMRPCFWVELIRGRPKENTIWTSGSSISFCGVNSDTVGWSWPDGAELPFTIDK
    
    

    Submitting a genome annotation job

    1. Submit annotation job

    $ p3-submit-genome-annotation --contigs-file influenza_11320.435309.fasta \
    --taxonomy-id 11320 --scientific-name "Influenza A virus" \
    /isingh@patricbrc.org/home t3
    Uploading influenza_11320.435309.fasta to /isingh@patricbrc.org/home/influenza_11320.435309.fasta (1.0 Kbytes)...
    done
    Submitted annotation with id 10940738
    

    2. View Listing of job’s output folder

    $ p3-ls -l /isingh@patricbrc.org/home/.t3/
    Srw-- isingh@patricbrc.org  13009 Jun 20 21:14 GenomeReport.html
    Srw-- isingh@patricbrc.org  27758 Jun 20 21:14 genome_quality_details.txt
    

    3. Download output of your job

    $ p3-cp -r ws:/isingh@patricbrc.org/home/.t3 .
    mkdir ./.t3
    Copy ws:/isingh@patricbrc.org/home/.t3/genome_quality_details.txt to ./.t3/genome_quality_details.txt
    Copy ws:/isingh@patricbrc.org/home/.t3/GenomeReport.html to ./.t3/GenomeReport.html
    Copy ws:/isingh@patricbrc.org/home/.t3/t3.genome to ./.t3/t3.genome
    Copy ws:/isingh@patricbrc.org/home/.t3/t3.contigs.fasta to ./.t3/t3.contigs.fasta
    Copy ws:/isingh@patricbrc.org/home/.t3/t3.feature_dna.fasta to ./.t3/t3.feature_dna.fasta