Sequencing of Influenza A and Influenza B Viruses

Sequencing of Influenza A and Influenza B Viruses

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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.
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The effective rate of influenza reassortment is limited during human infection.
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Potential for Low-Pathogenic Avian H7 Influenza A Viruses To Replicate and Cause Disease in a Mammalian Model.
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Deep Sequencing of Influenza A Virus from a Human Challenge Study Reveals a Selective Bottleneck and Only Limited Intrahost Genetic Diversification.
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Introduction, Evolution, and Dissemination of Influenza A Viruses in Exhibition Swine in the United States during 2009 to 2013.
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A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses.
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The administration of intranasal live attenuated influenza vaccine induces changes in the nasal microbiota and nasal epithelium gene expression profiles.
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The Journal of general virology. 2015-08-01; 96.8: 2050-60.
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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.
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Diversifying Selection Analysis Predicts Antigenic Evolution of 2009 Pandemic H1N1 Influenza A Virus in Humans.
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Spread and persistence of influenza A viruses in waterfowl hosts in the North American Mississippi migratory flyway.
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Correction for Joseph et al., Adaptation of pandemic H2N2 influenza A viruses in humans.
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Global migration of influenza A viruses in swine.
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A RESTful API for Access to Phylogenetic Tools via the CIPRES Science Gateway.
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Toward a method for tracking virus evolutionary trajectory applied to the pandemic H1N1 2009 influenza virus.
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Characterization of uncultivable bat influenza virus using a replicative synthetic virus.
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Introductions and evolution of human-origin seasonal influenza a viruses in multinational swine populations.
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The evolutionary dynamics of influenza A and B viruses in the tropical city of Managua, Nicaragua.
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Analysis of recombinant H7N9 wild-type and mutant viruses in pigs shows that the Q226L mutation in HA is important for transmission.
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Universal influenza B virus genomic amplification facilitates sequencing, diagnostics, and reverse genetics.
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North Atlantic migratory bird flyways provide routes for intercontinental movement of avian influenza viruses.
PloS one. 2014-01-01; 9.6: e92075.
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Metadata-driven comparative analysis tool for sequences (meta-CATS): an automated process for identifying significant sequence variations that correlate with virus attributes.
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Sequencing viral genomes from a single isolated plaque.
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Asparagine substitution at PB2 residue 701 enhances the replication, pathogenicity, and transmission of the 2009 pandemic H1N1 influenza A virus.
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A robust tool highlights the influence of bird migration on influenza A virus evolution.
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VIGOR extended to annotate genomes for additional 12 different viruses.
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Influenza A virus molecular virology techniques.
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Metagenomic analysis of RNA viruses in a fresh water lake.
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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.