scholarly journals Identification and Characterization of Swine Influenza Virus H1N1 Variants Generated in Vaccinated and Nonvaccinated, Challenged Pigs

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2087
Author(s):  
Álvaro López-Valiñas ◽  
Marta Sisteré-Oró ◽  
Sergi López-Serrano ◽  
Laura Baioni ◽  
Ayub Darji ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza Pandemic ◽  
Viral Evolution ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Viral Fitness ◽  
Ns1 Protein ◽  
Trivalent Vaccine

Influenza viruses represent a continuous threat to both animal and human health. The 2009 H1N1 A influenza pandemic highlighted the importance of a swine host in the adaptation of influenza viruses to humans. Nowadays, one of the most extended strategies used to control swine influenza viruses (SIVs) is the trivalent vaccine application, whose formulation contains the most frequently circulating SIV subtypes H1N1, H1N2, and H3N2. These vaccines do not provide full protection against the virus, allowing its replication, evolution, and adaptation. To better understand the main mechanisms that shape viral evolution, here, the SIV intra-host diversity was analyzed in samples collected from both vaccinated and nonvaccinated animals challenged with the H1N1 influenza A virus. Twenty-eight whole SIV genomes were obtained by next-generation sequencing, and differences in nucleotide variants between groups were established. Substitutions were allocated along all influenza genetic segments, while the most relevant nonsynonymous substitutions were allocated in the NS1 protein on samples collected from vaccinated animals, suggesting that SIV is continuously evolving despite vaccine application. Moreover, new viral variants were found in both vaccinated and nonvaccinated pigs, showing relevant substitutions in the HA, NA, and NP proteins, which may increase viral fitness under field conditions.

scholarly journals Cocirculation of Swine H1N1 Influenza A Virus Lineages in Germany

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 762 ◽  
Author(s):  
Roland Zell ◽  
Marco Groth ◽  
Andi Krumbholz ◽  
Jeannette Lange ◽  
Anja Philipps ◽  
...  
Keyword(s):  
Influenza A ◽  
Antigenic Variation ◽  
Phylogenetic Analyses ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Influenza Surveillance ◽  
Northwest Germany

The genome analysis of 328 H1N1 swine influenza virus isolates collected in a 13-year long-term swine influenza surveillance in Germany is reported. Viral genomes were sequenced with the Illumina next-generation sequencing technique and conventional Sanger methods. Phylogenetic analyses were conducted with Bayesian tree inference. The results indicate continued prevalence of Eurasian avian swine H1N1 but also emergence of a novel H1N1 reassortant, named Schneiderkrug/2013-like swine H1N1, with human-like hemagglutinin and avian-like neuraminidase and internal genes. Additionally, the evolution of an antigenic drift variant of A (H1N1) pdm09 was observed, named Wachtum/2014-like swine H1N1. Both variants were first isolated in northwest Germany, spread to neighboring German states and reached greater proportions of the H1N1 isolates of 2014 and 2015. The upsurge of Wachtum/2014-like swine H1N1 is of interest as this is the first documented persistent swine-to-swine spread of A (H1N1) pdm09 in Germany associated with antigenic variation. Present enzootic swine influenza viruses in Germany now include two or more co-circulating, antigenically variant viruses of each of the subtypes, H1N1 and H1N2.

scholarly journals Mutations in the NS1 Protein of Swine Influenza Virus Impair Anti-Interferon Activity and Confer Attenuation in Pigs

2005 ◽  
Vol 79 (12) ◽  
pp. 7535-7543 ◽  
Author(s):  
Alicia Solórzano ◽  
Richard J. Webby ◽  
Kelly M. Lager ◽  
Bruce H. Janke ◽  
Adolfo García-Sastre ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Nonstructural Protein ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Model Systems ◽  
Ns1 Protein ◽  
Wild Type ◽  
Virulence Attenuation

ABSTRACT It has been shown previously that the nonstructural protein NS1 of influenza virus is an alpha/beta interferon (IFN-α/β) antagonist, both in vitro and in experimental animal model systems. However, evidence of this function in a natural host has not yet been obtained. Here we investigated the role of the NS1 protein in the virulence of a swine influenza virus (SIV) isolate in pigs by using reverse genetics. The virulent wild-type A/Swine/Texas/4199-2/98 (TX/98) virus and various mutants encoding carboxy-truncated NS1 proteins were rescued. Growth properties of TX/98 viruses with mutated NS1, induction of IFN in tissue culture, and virulence-attenuation in pigs were analyzed and compared to those of the recombinant wild-type TX/98 virus. Our results indicate that deletions in the NS1 protein decrease the ability of the TX/98 virus to prevent IFN-α/β synthesis in pig cells. Moreover, all NS1 mutant viruses were attenuated in pigs, and this correlated with the amount of IFN-α/β induced in vitro. These data suggest that the NS1 protein of SIV is a virulence factor. Due to their attenuation, NS1-mutated swine influenza viruses might have a great potential as live attenuated vaccine candidates against SIV infections of pigs.

scholarly journals The evolutionary dynamics of influenza A virus adaptation to mammalian hosts

2013 ◽  
Vol 368 (1614) ◽  
pp. 20120382 ◽  
Author(s):  
S. Bhatt ◽  
T. T. Lam ◽  
S. J. Lycett ◽  
A. J. Leigh Brown ◽  
T. A. Bowden ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Adaptive Evolution ◽  
Influenza A ◽  
Evolutionary Dynamics ◽  
Adaptive Dynamics ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Viral Fitness ◽  
Influenza A Viruses ◽  
Entire Genome

Few questions on infectious disease are more important than understanding how and why avian influenza A viruses successfully emerge in mammalian populations, yet little is known about the rate and nature of the virus’ genetic adaptation in new hosts. Here, we measure, for the first time, the genomic rate of adaptive evolution of swine influenza viruses (SwIV) that originated in birds. By using a curated dataset of more than 24 000 human and swine influenza gene sequences, including 41 newly characterized genomes, we reconstructed the adaptive dynamics of three major SwIV lineages (Eurasian, EA; classical swine, CS; triple reassortant, TR). We found that, following the transfer of the EA lineage from birds to swine in the late 1970s, EA virus genes have undergone substantially faster adaptive evolution than those of the CS lineage, which had circulated among swine for decades. Further, the adaptation rates of the EA lineage antigenic haemagglutinin and neuraminidase genes were unexpectedly high and similar to those observed in human influenza A. We show that the successful establishment of avian influenza viruses in swine is associated with raised adaptive evolution across the entire genome for many years after zoonosis, reflecting the contribution of multiple mutations to the coordinated optimization of viral fitness in a new environment. This dynamics is replicated independently in the polymerase genes of the TR lineage, which established in swine following separate transmission from non-swine hosts.

scholarly journals Resurrected ancestral influenza A viruses recapitulate the avian-to-mammalian adaptation of European avian-like swine influenza virus

2021 ◽  
Author(s):  
Wen Su ◽  
Rhodri Harfoot ◽  
Yvonne Su ◽  
Jennifer DeBeauchamp ◽  
Udayan Joseph ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Polymerase Activity ◽  
Influenza Viruses ◽  
Mammalian Host ◽  
Influenza A Viruses ◽  
Sequence Reconstruction

Abstract The emergence of a pandemic influenza virus may be better anticipated if we better understand the evolutionary steps taken by avian influenza viruses as they adapt to mammals. We used ancestral sequence reconstruction to resurrect viruses representing initial adaptive stages of the European avian-like H1N1 virus as it transitioned from avian to swine hosts. We demonstrate that efficient transmissibility in pigs was gained through stepwise adaptation after 1983. These time-dependent adaptations resulted in changes in hemagglutinin receptor binding specificity and increased viral polymerase activity. An NP-R351K mutation under strong positive selection increased the transmissibility of a reconstructed virus. The stepwise-adaptation of a wholly avian influenza virus to a mammalian host suggests a window where targeted intervention may have highest impact. Successful intervention will, however, require strategic coordination of surveillance and risk assessment activities to identify these adapting viruses and guide pandemic preparedness resources.

scholarly journals Influenza at the animal–human interface: a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1)

2014 ◽  
Vol 19 (18) ◽  
Author(s):  
G S Freidl ◽  
A Meijer ◽  
E de Bruin ◽  
M de Nardi ◽  
O Munoz ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Human Infection ◽  
Influenza Viruses ◽  
Diagnostic Methods ◽  
World Health ◽  
Review Of The Literature

Factors that trigger human infection with animal influenza virus progressing into a pandemic are poorly understood. Within a project developing an evidence-based risk assessment framework for influenza viruses in animals, we conducted a review of the literature for evidence of human infection with animal influenza viruses by diagnostic methods used. The review covering Medline, Embase, SciSearch and CabAbstracts yielded 6,955 articles, of which we retained 89; for influenza A(H5N1) and A(H7N9), the official case counts of the World Health Organization were used. An additional 30 studies were included by scanning the reference lists. Here, we present the findings for confirmed infections with virological evidence. We found reports of 1,419 naturally infected human cases, of which 648 were associated with avian influenza virus (AIV) A(H5N1), 375 with other AIV subtypes, and 396 with swine influenza virus (SIV). Human cases naturally infected with AIV spanned haemagglutinin subtypes H5, H6, H7, H9 and H10. SIV cases were associated with endemic SIV of H1 and H3 subtype descending from North American and Eurasian SIV lineages and various reassortants thereof. Direct exposure to birds or swine was the most likely source of infection for the cases with available information on exposure.

scholarly journals The NS1 protein of influenza A virus suppresses interferon-regulated activation of antigen-presentation and immune-proteasome pathways

2011 ◽  
Vol 92 (9) ◽  
pp. 2093-2104 ◽  
Author(s):  
Jennifer R. Tisoncik ◽  
Rosalind Billharz ◽  
Svetlana Burmakina ◽  
Sarah E. Belisle ◽  
Sean C. Proll ◽  
...  
Keyword(s):  
Gene Expression ◽  
Antigen Presentation ◽  
Influenza A ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Mutant Virus ◽  
Type I ◽  
Ns1 Protein ◽  
Effector Domain ◽  
Regulated Gene Expression

The NS1 protein of influenza virus counters host antiviral defences primarily by antagonizing the type I interferon (IFN) response. Both the N-terminal dsRNA-binding domain and the C-terminal effector domain are required for optimal suppression of host responses during infection. To better understand the regulatory role of the NS1 effector domain, we used an NS1-truncated mutant virus derived from human H1N1 influenza isolate A/Texas/36/91 (Tx/91) and assessed global transcriptional profiles from two independent human lung cell-culture models. Relative to the wild-type Tx/91-induced gene expression, the NS1 mutant virus induced enhanced expression of innate immune genes, specifically NF-κB signalling-pathway genes and IFN-α and -β target genes. We queried an experimentally derived IFN gene set to gauge the proportion of IFN-responsive genes that are suppressed specifically by NS1. We show that the C-terminally truncated NS1 mutant virus is less efficient at suppressing IFN-regulated gene expression associated with activation of antigen-presentation and immune-proteasome pathways. This is the first report integrating genomic analysis from two independent human culture systems, including primary lung cells, using genetically similar H1N1 influenza viruses that differ only in the length of the NS1 protein.

scholarly journals A single dose vaccination with an elastase-dependent H1N1 live attenuated swine influenza virus protects pigs from challenge with 2009 pandemic H1N1 virus

2014 ◽  
Vol 64 (1) ◽  
pp. 10-23
Author(s):  
Aleksandar Mašić ◽  
Niziti Woldeab ◽  
Carissa Embury-Hyatt ◽  
Yan Zhou ◽  
Shawn Babiuk
Keyword(s):  
Influenza Virus ◽  
Single Dose ◽  
Influenza A Virus ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Virus Infections ◽  
Intranasal Route

Abstract The 2009 outbreak of H1N1 influenza A viruses in humans underscored the importance of pigs in influenza A virus evolution and the emergence of novel viruses with pandemic potential. In addition, influenza A virus infections continued to cause production losses in the agricultural industry resulting in a significant drop of profit. The primary method to control influenza A virus infections in pigs is through vaccination. Previously we demonstrated that two doses of an elastase-dependent live attenuated swine influenza virus administered by either the intratracheal or intranasal route can provide a high degree of protection in pigs against challenge with both homologous and different heterologous swine influenza viruses. Here we report the protection efficacy of a single dose elastase-dependent live attenuated swine influenza virus administered by the intranasal route against challenge with homologous subtypic H1N1 2009 pandemic swine-like influenza virus. Protection was observed in the absence of neutralizing antibodies specific for H1N1 2009 in sera.

scholarly journals Dual R108K and G189D Mutations in the NS1 Protein of A/H1N1 Influenza Virus Counteract Host Innate Immune Responses

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 905
Author(s):  
Meng-Ting Huang ◽  
Sen Zhang ◽  
Ya-Nan Wu ◽  
Wei Li ◽  
Yu-Chang Li ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Nonstructural Protein ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Innate Immune ◽  
Ns1 Protein ◽  
H1n1 Influenza Virus ◽  
Functional Sites ◽  
Nonstructural Protein 1

Influenza A viruses (IAV) modulate host antiviral responses to promote growth and pathogenicity. Here, we examined the multifunctional IAV nonstructural protein 1 (NS1) of influenza A virus to better understand factors that contribute to viral replication efficiency or pathogenicity. In 2009, a pandemic H1N1 IAV (A/California/07/2009 pH1N1) emerged in the human population from swine. Seasonal variants of this virus are still circulating in humans. Here, we compared the sequence of a seasonal variant of this H1N1 influenza virus (A/Urumqi/XJ49/2018(H1N1), first isolated in 2018) with the pandemic strain A/California/07/2009. The 2018 virus harbored amino acid mutations (I123V and N205S) in important functional sites; however, 108R and 189G were highly conserved between A/California/07/2009 and the 2018 variant. To better understand interactions between influenza viruses and the human innate immune system, we generated and rescued seasonal 2009 H1N1 IAV mutants expressing an NS1 protein harboring a dual mutation (R108K/G189D) at these conserved residues and then analyzed its biological characteristics. We found that the mutated NS1 protein exhibited systematic and selective inhibition of cytokine responses via a mechanism that may not involve binding to cleavage and polyadenylation specificity factor 30 (CPSF30). These results highlight the complexity underlying host–influenza NS1 protein interactions.

scholarly journals The global antigenic diversity of swine influenza A viruses

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Nicola S Lewis ◽  
Colin A Russell ◽  
Pinky Langat ◽  
Tavis K Anderson ◽  
Kathryn Berger ◽  
...  
Keyword(s):  
Influenza A ◽  
Disease Burden ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Antigenic Diversity ◽  
Continental Scale ◽  
Pandemic Threat ◽  
Different Parts

Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigenic diversity shapes the risk profile of swine influenza viruses in terms of their epizootic and pandemic potential. Here, using the most comprehensive set of swine influenza virus antigenic data compiled to date, we quantify the antigenic diversity of swine influenza viruses on a multi-continental scale. The substantial antigenic diversity of recently circulating viruses in different parts of the world adds complexity to the risk profiles for the movement of swine and the potential for swine-derived infections in humans.

scholarly journals Identification, Genetic Analysis, and Pathogenicity of Classical Swine H1N1 and Human-Swine Reassortant H1N1 Influenza Viruses from Pigs in China

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 55 ◽  
Author(s):  
Yafen Song ◽  
Yong Zhang ◽  
Bing Zhang ◽  
Ling Chen ◽  
Min Zhang ◽  
...  
Keyword(s):  
Phylogenetic Analyses ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Swine Industry ◽  
Ha Gene ◽  
Lethal Infection ◽  
Duration Of Infection ◽  
Imminent Threat

Swine influenza virus causes a substantial disease burden to swine populations worldwide and poses an imminent threat to the swine industry and humans. Given its importance, we characterized two swine influenza viruses isolated from Shandong, China. The homology and phylogenetic analyses showed that all eight gene segments of A/swine/Shandong/AV1522/2011(H1N1) were closely related to A/Maryland/12/1991(H1N1) circulating in North America. The HA, NA, M, and NS genes of the isolate were also confirmed to have a high homology to A/swine/Hubei/02/2008(H1N1) which appeared in China in 2008, and the virus was clustered into the classical swine lineage. The gene segments of A/swine/Shandong/AV1523/2011(H1N1) were highly homologous to the early human H1N1 and H2N2 influenza viruses, except for the HA gene, and the virus was a reassortant H1N1 virus containing genes from the classical swine (HA) and human (NA, PB2, PB1, PA, NP, M, and NS) lineages. Both the viruses could cause lethal infection and replicate efficiently in the lungs, brains, spleens, and kidneys of mice. Histopathological examinations showed that AV1522 and AV1523 viruses caused a spectrum of marked pneumonia and meningoencephalitis according to the duration of infection, demonstrating a progression of respiratory disease and neurological disease over the course of infection that ultimately resulted in lethality for the infected mice. The changes in the pathogenicity of swine influenza viruses to mammals, accompanied with the continuous reassortment and evolution of the viruses, highlights the importance of ongoing epidemiological investigation.

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