Genomics of Influenza A and Influenza B Viruses

Influenza viruses are members of the Orthomyxoviridae family whose genomes consist of 8 segments of single-stranded negative-sense RNA. Influenza A virus (IAV) and influenza B virus (IBV) are responsible for seasonal epidemics of respiratory illness among humans. While IBV circulates only among humans, IAV circulates among many mammalian and avian hosts. Global surveillance of these viruses is necessary for maintaining a well-matched annual influenza vaccine, as well as for detecting the emergence of new influenza strains that may cause a human pandemic. Hemagglutinin (HA) and neuraminidase (NA) are the two predominant viral glycoproteins found in the viral envelope, and are the primary targets of the host immune system and are key factors in the entry and exit of influenza particles from host cells. HA and NA are also used to classify influenza A viruses into subtypes (e.g., H3N2, H5N1).

Our collaborative influenza projects: 1) characterizing the temporal and spatial evolutionary dynamics of the IAV and IBV circulating globally in humans and wild birds, 2) identifying the IAV genotypes circulating in pigs at county fairs (swine-human interface) to determine if fairs produce novel reassortants or enable zoonosis/reverse zoonosis, 3) determining if specific internal gene segment constellations enhance viral fitness, 4) detecting epistatic interactions between gene segments, and 5) assessing the impact of inter-hemispheric migration of viruses/gene segments.

The accumulation of mutations at antigenic sites (antigenic drift) and the reassortment of segments with differing evolutionary histories (antigenic shift) allow influenza viruses to continually evade the host immune response. Annual human epidemics are currently caused by two IAV subtypes (A/H3N2, A/H1N1) and by two diverging IBV lineages (B/Yamagata, B/Victoria). IAVs circulating in avian and swine hosts are also important because of frequent interspecies transmission, which periodically causes human pandemics (e.g., pandemics of 1957, 1968, and 2009). Complete genome sequencing is required to identify fitness advantages conferred by genes and how antigenic drift in HA/NA drive mutations throughout the genome. Genomic sequence data will be generated from the diverse subtypes/strains (H1-H16, N1-N9) in avian reservoirs, which are a source of viruses with pandemic potential (e.g., H5N1). Swine are 'mixing vessels' for reassortment between avian and human viruses because they express sialic acid molecules that act as receptors for both avian and human viruses. Human, avian, and classical swine lineage viruses are co-circulating in North American swine populations, generating novel reassortants and leading to hundreds of zoonotic infections (e.g., H3N2v). The large number of co-circulating viruses in swine is the most genetically dynamic situation observed in North America over the last 90 years.


Pathogenicity of modified bat influenza virus with different M genes and its reassortment potential with swine influenza A virus.
The Journal of general virology. 2017-04-01; 98.4: 577-584.
PMID: 28100299
The blood DNA virome in 8,000 humans.
PLoS pathogens. 2017-03-22; 13.3: e1006292.
PMID: 28328962
The effective rate of influenza reassortment is limited during human infection.
PLoS pathogens. 2017-02-01; 13.2: e1006203.
PMID: 28170438
Potential for Low-Pathogenic Avian H7 Influenza A Viruses To Replicate and Cause Disease in a Mammalian Model.
Journal of virology. 2017-02-01; 91.3:
PMID: 27852855
Deep Sequencing of Influenza A Virus from a Human Challenge Study Reveals a Selective Bottleneck and Only Limited Intrahost Genetic Diversification.
Journal of virology. 2016-12-15; 90.24: 11247-11258.
PMID: 27707932
Introduction, Evolution, and Dissemination of Influenza A Viruses in Exhibition Swine in the United States during 2009 to 2013.
Journal of virology. 2016-12-01; 90.23: 10963-10971.
PMID: 27681134
A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses.
mSphere. 2016-11-01; 1.6:
PMID: 27981236
Reversion of Cold-Adapted Live Attenuated Influenza Vaccine into a Pathogenic Virus.
Journal of virology. 2016-10-01; 90.19: 8454-63.
PMID: 27440882
Ecosystem Interactions Underlie the Spread of Avian Influenza A Viruses with Pandemic Potential.
PLoS pathogens. 2016-05-01; 12.5: e1005620.
PMID: 27166585
Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States.
Journal of virology. 2016-02-15; 90.4: 1997-2007.
PMID: 26656685
Quantifying influenza virus diversity and transmission in humans.
Nature genetics. 2016-02-01; 48.2: 195-200.
PMID: 26727660
Evolutionary Dynamics of Influenza A Viruses in US Exhibition Swine.
The Journal of infectious diseases. 2016-01-15; 213.2: 173-82.
PMID: 26243317
The administration of intranasal live attenuated influenza vaccine induces changes in the nasal microbiota and nasal epithelium gene expression profiles.
Microbiome. 2015-12-15; 3.74.
PMID: 26667497
Differential Susceptibilities of Human Lung Primary Cells to H1N1 Influenza Viruses.
Journal of virology. 2015-12-01; 89.23: 11935-44.
PMID: 26378172
The soft palate is an important site of adaptation for transmissible influenza viruses.
Nature. 2015-10-01; 526.7571: 122-5.
PMID: 26416728
Evolution of Influenza B Virus in Kuala Lumpur, Malaysia, between 1995 and 2008.
Journal of virology. 2015-09-01; 89.18: 9689-92.
PMID: 26136576
Influenza A virus evolution and spatio-temporal dynamics in Eurasian wild birds: a phylogenetic and phylogeographical study of whole-genome sequence data.
The Journal of general virology. 2015-08-01; 96.8: 2050-60.
PMID: 25904147
Equine and Canine Influenza H3N8 Viruses Show Minimal Biological Differences Despite Phylogenetic Divergence.
Journal of virology. 2015-07-01; 89.13: 6860-73.
PMID: 25903329
Long-term surveillance of H7 influenza viruses in American wild aquatic birds: are the H7N3 influenza viruses in wild birds the precursors of highly pathogenic strains in domestic poultry?
Emerging microbes & infections. 2015-06-17; 4.e35.
PMID: 26954883
Haemagglutinin mutations and glycosylation changes shaped the 2012/13 influenza A(H3N2) epidemic, Houston, Texas.
Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. 2015-05-07; 20.18:
PMID: 25990233
Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1 Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to Increased MIP-2 Expression.
Journal of virology. 2015-05-01; 89.10: 5651-67.
PMID: 25762737
Diversifying Selection Analysis Predicts Antigenic Evolution of 2009 Pandemic H1N1 Influenza A Virus in Humans.
Journal of virology. 2015-05-01; 89.10: 5427-40.
PMID: 25741011
Spread and persistence of influenza A viruses in waterfowl hosts in the North American Mississippi migratory flyway.
Journal of virology. 2015-05-01; 89.10: 5371-81.
PMID: 25741003
Correction for Joseph et al., Adaptation of pandemic H2N2 influenza A viruses in humans.
Journal of virology. 2015-04-01; 89.8: 4706.
PMID: 25792756
Global migration of influenza A viruses in swine.
Nature communications. 2015-03-27; 6.6696.
PMID: 25813399
A RESTful API for Access to Phylogenetic Tools via the CIPRES Science Gateway.
Evolutionary bioinformatics online. 2015-01-01; 11.43-8.
PMID: 25861210
Toward a method for tracking virus evolutionary trajectory applied to the pandemic H1N1 2009 influenza virus.
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2014-12-01; 28.351-7.
PMID: 25064525
Characterization of uncultivable bat influenza virus using a replicative synthetic virus.
PLoS pathogens. 2014-10-01; 10.10: e1004420.
PMID: 25275541
Introductions and evolution of human-origin seasonal influenza a viruses in multinational swine populations.
Journal of virology. 2014-09-01; 88.17: 10110-9.
PMID: 24965467
The evolutionary dynamics of influenza A and B viruses in the tropical city of Managua, Nicaragua.
Virology. 2014-08-01; 462-463.81-90.
PMID: 24959982
Analysis of recombinant H7N9 wild-type and mutant viruses in pigs shows that the Q226L mutation in HA is important for transmission.
Journal of virology. 2014-07-01; 88.14: 8153-65.
PMID: 24807722
Universal influenza B virus genomic amplification facilitates sequencing, diagnostics, and reverse genetics.
Journal of clinical microbiology. 2014-05-01; 52.5: 1330-7.
PMID: 24501036
North Atlantic migratory bird flyways provide routes for intercontinental movement of avian influenza viruses.
PloS one. 2014-01-01; 9.3: e92075.
PMID: 24647410
Metadata-driven comparative analysis tool for sequences (meta-CATS): an automated process for identifying significant sequence variations that correlate with virus attributes.
Virology. 2013-12-01; 447.1-2: 45-51.
PMID: 24210098
Sequencing viral genomes from a single isolated plaque.
Virology journal. 2013-06-06; 10.181.
PMID: 23742765
Asparagine substitution at PB2 residue 701 enhances the replication, pathogenicity, and transmission of the 2009 pandemic H1N1 influenza A virus.
PloS one. 2013-01-01; 8.5: e67616.
PMID: 23799150
A robust tool highlights the influence of bird migration on influenza A virus evolution.
Molecular ecology. 2012-12-01; 21.24: 5905-7.
PMID: 23355978
VIGOR extended to annotate genomes for additional 12 different viruses.
Nucleic acids research. 2012-07-01; 40.Web Server issue: W186-92.
PMID: 22669909
Large-scale sequencing and the natural history of model human RNA viruses.
Future virology. 2012-06-01; 7.6: 563-573.
PMID: 23682295
Influenza A virus molecular virology techniques.
Methods in molecular biology (Clifton, N.J.). 2012-01-01; 944.175-92.
PMID: 22528160
Metagenomic analysis of RNA viruses in a fresh water lake.
PloS one. 2009-09-29; 4.9: e7264.
PMID: 19787045


This project has been funded in whole or part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under Award Numbers N01-AI30071 and U19AI110819.

Principal Investigator

Key Staff

  • Torrey Williams


Ian Barr, PhD

Aubree Gordon, PhD

Jonathan Runstadler, PhD

Richard Slemons, PhD

David Stallknecht, PhD

Andrew Bowman, PhD

Susan Detmer, PhD

Stacey Schultz-Cherry, PhD

Kirsten St. George, PhD

Related Research