scholarly journals NAction! How Can Neuraminidase-Based Immunity Contribute to Better Influenza Virus Vaccines?

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Florian Krammer ◽  
Ron A. M. Fouchier ◽  
Maryna C. Eichelberger ◽  
Richard J. Webby ◽  
Kathryn Shaw-Saliba ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Vaccine Development ◽  
Protective Role ◽  
National Institutes Of Health ◽  
Antigenic Drift ◽  
Centers Of Excellence ◽  
Open Questions ◽  
Infection Mechanisms

ABSTRACTNeuraminidase is one of the two surface glycoproteins of influenza A and B viruses. It has enzymatic activity that cleaves terminal sialic acid from glycans, and that activity is essential at several points in the virus life cycle. While neuraminidase is a major target for influenza antivirals, it is largely ignored in vaccine development. Current inactivated influenza virus vaccines might contain neuraminidase, but the antigen quantity and quality are varied and not standardized. While there are data that show a protective role of anti-neuraminidase immunity, many questions remain unanswered. These questions, among others, concern the targeted epitopes or antigenic sites, the potential for antigenic drift, and, connected to that, the breadth of protection, differences in induction of immune responses by vaccination versus infection, mechanisms of protection, the role of mucosal antineuraminidase antibodies, stability, and the immunogenicity of neuraminidase in vaccine formulations. Reagents for analysis of neuraminidase-based immunity are scarce, and assays are not widely used for clinical studies evaluating vaccines. However, efforts to better understand neuraminidase-based immunity have been made recently. A neuraminidase focus group, NAction!, was formed at a Centers of Excellence for Influenza Research and Surveillance meeting at the National Institutes of Health in Bethesda, MD, to promote research that helps to understand neuraminidase-based immunity and how it can contribute to the design of better and broadly protective influenza virus vaccines. Here, we review open questions and knowledge gaps that have been identified by this group and discuss how the gaps can be addressed, with the ultimate goal of designing better influenza virus vaccines.

A Fungal Cu/Zn-Containing Superoxide Dismutase Enhances the Therapeutic Efficacy of a Plant Polyphenol Extract in Experimental Influenza Virus Infection

2010 ◽  
Vol 65 (5-6) ◽  
pp. 419-428 ◽  
Author(s):  
Julia Serkedjieva ◽  
Tsvetanka Stefanova ◽  
Ekaterina Krumova
Keyword(s):  
Superoxide Dismutase ◽  
Influenza Virus ◽  
Virus Infection ◽  
Protective Effect ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Protective Role ◽  
Combined Application ◽  
Combined Use ◽  
Experimental Influenza

The combined protective effect of a polyphenol-rich extract, isolated from Geranium sanguineum L. (PC), and a novel naturally glycosylated Cu/Zn-containing superoxide dismutase, produced from the fungal strain Humicula lutea 103 (HL-SOD), in the experimental influenza A virus infection (EIVI) in mice, induced with the virus A/Aichi/2/68 (H3N2), was investigated. The combined application of HL-SOD and PC in doses, which by themselves do not defend significantly mice in EIVI, resulted in a synergistically increased protection, determined on the basis of protective indices and amelioration of lung injury. Lung weights and consolidation as well as infectious lung virus titers were all decreased significantly parallel to the reduction of the mortality rates; lung indices were raised. The excessive production of reactive oxygen species (ROS) by alveolar macrophages (aMØ) as well as the elevated levels of the lung antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), induced by EIVI, were brought to normal. For comparative reasons the combined protective effect of PC and vitamin C was investigated. The obtained results support the combined use of antioxidants for the treatment of influenza virus infection and in general indicate the beneficial protective role of combinations of viral inhibitors of natural origin with diverse modes of action.

scholarly journals Polymerase Acidic Subunit of H9N2 Polymerase Complex Induces Cell Apoptosis by Binding to PDCD 7 in A549 Cells

2020 ◽  
Author(s):  
Shaohua Wang ◽  
Na Li ◽  
Shugang Jin ◽  
Ruihua Zhang ◽  
Tong Xu
Keyword(s):  
Cell Death ◽  
Influenza Virus ◽  
Cell Apoptosis ◽  
Influenza A ◽  
A549 Cells ◽  
Influenza Virus Infection ◽  
Economic Loss ◽  
Poultry Production ◽  
H9n2 Influenza Virus

Abstract Background: H9N2 influenza virus, a subtype of influenza A virus, can spread across different species and induce the respiratory infectious disease in humans, leading to a severe public health risk and a huge economic loss to poultry production. Increasing studies have shown that polymerase acidic (PA) subunit of RNA polymerase in ribonucleoproteins complex of H9N2 involves in crossing the host species barriers, the replication and airborne transmission of H9N2.Methods: Here, to further investigate the role of PA subunit during the infection of H9N2 influenza virus, we employed mass spectrometry (MS) to search the potential binding proteins of PA subunit of H9N2. Our MS results showed that programmed cell death protein 7 (PDCD7) is a binding target of PA subunit. Co-immunoprecipitation and pull-down assays further confirmed the interaction between PDCD7 and PA subunit. Overexpression of PA subunit in A549 lung cells greatly increased the levels of PDCD7 in the nuclear and induced cell death assayed by MTT assay.Results: Flow cytometry analysis and Western blot results showed that PA subunit overexpression significantly increased the expression of pro-apoptotic protein, bax and caspase 3, and induced cell apoptosis. However, knockout of PDCD7 effectively attenuated the effects of PA overexpression in cell apoptosis.Conclusions: In conclusion, the PA subunit of H9N2 bind with PDCD7 and regulated cell apoptosis, which provide new insights in the role of PA subunit during H9N2 influenza virus infection.

scholarly journals Spatiotemporal Distribution and Evolution of the A/H1N1 2009 Pandemic Influenza Virus in Pigs in France from 2009 to 2017: Identification of a Potential Swine-Specific Lineage

2018 ◽  
Vol 92 (24) ◽  
Author(s):  
Amélie Chastagner ◽  
Séverine Hervé ◽  
Emilie Bonin ◽  
Stéphane Quéguiner ◽  
Edouard Hirchaud ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Phylogenetic Analyses ◽  
Swine Influenza ◽  
H1n1 Influenza ◽  
Antigenic Drift ◽  
Influenza A Viruses ◽  
Evolutionary Patterns ◽  
Increased Risk ◽  
Na Sequences

ABSTRACT The H1N1 influenza virus responsible for the most recent pandemic in 2009 (H1N1pdm) has spread to swine populations worldwide while it replaced the previous seasonal H1N1 virus in humans. In France, surveillance of swine influenza A viruses in pig herds with respiratory outbreaks led to the detection of 44 H1N1pdm strains between 2009 and 2017, regardless of the season, and findings were not correlated with pig density. From these isolates, 17 whole-genome sequences were obtained, as were 6 additional hemagglutinin (HA)/neuraminidase (NA) sequences, in order to perform spatial and temporal analyses of genetic diversity and to compare evolutionary patterns of H1N1pdm in pigs to patterns for human strains. Following mutation accumulation and fixation over time, phylogenetic analyses revealed for the first time the divergence of a swine-specific genogroup within the H1N1pdm lineage. The divergence is thought to have occurred around 2011, although this was demonstrated only through strains isolated in 2015 to 2016 in the southern half of France. To date, these H1N1pdm swine strains have not been related to any increased virulence in swine herds and have not exhibited any antigenic drift compared to seasonal human strains. However, further monitoring is encouraged, as diverging evolutionary patterns in these two species, i.e., swine and humans, may lead to the emergence of viruses with a potentially higher risk to both animal and human health.IMPORTANCE Pigs are a “mixing vessel” for influenza A viruses (IAVs) because of their ability to be infected by avian and human IAVs and their propensity to facilitate viral genomic reassortment events. Also, as IAVs may evolve differently in swine and humans, pigs can become a reservoir for old human strains against which the human population has become immunologically naive. Thus, viruses from the novel swine-specific H1N1pdm genogroup may continue to diverge from seasonal H1N1pdm strains and/or from other H1N1pdm viruses infecting pigs and lead to the emergence of viruses that would not be covered by human vaccines and/or swine vaccines based on antigens closely related to the original H1N1pdm virus. This discovery confirms the importance of encouraging swine IAV monitoring because H1N1pdm swine viruses could carry an increased risk to both human and swine health in the future as a whole H1N1pdm virus or gene provider in subsequent reassortant viruses.

scholarly journals Divergent Human-Origin Influenza Viruses Detected in Australian Swine Populations

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Frank Y. K. Wong ◽  
Celeste Donato ◽  
Yi-Mo Deng ◽  
Don Teng ◽  
Naomi Komadina ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Human Origin ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Data Set ◽  
Antigenic Properties

ABSTRACTGlobal swine populations infected with influenza A viruses pose a persistent pandemic risk. With the exception of a few countries, our understanding of the genetic diversity of swine influenza viruses is limited, hampering control measures and pandemic risk assessment. Here we report the genomic characteristics and evolutionary history of influenza A viruses isolated in Australia from 2012 to 2016 from two geographically isolated swine populations in the states of Queensland and Western Australia. Phylogenetic analysis with an expansive human and swine influenza virus data set comprising >40,000 sequences sampled globally revealed evidence of the pervasive introduction and long-term establishment of gene segments derived from several human influenza viruses of past seasons, including the H1N1/1977, H1N1/1995, H3N2/1968, and H3N2/2003, and the H1N1 2009 pandemic (H1N1pdm09) influenza A viruses, and a genotype that contained gene segments derived from the past three pandemics (1968, reemerged 1977, and 2009). Of the six human-derived gene lineages, only one, comprising two viruses isolated in Queensland during 2012, was closely related to swine viruses detected from other regions, indicating a previously undetected circulation of Australian swine lineages for approximately 3 to 44 years. Although the date of introduction of these lineages into Australian swine populations could not be accurately ascertained, we found evidence of sustained transmission of two lineages in swine from 2012 to 2016. The continued detection of human-origin influenza virus lineages in swine over several decades with little or unpredictable antigenic drift indicates that isolated swine populations can act as antigenic archives of human influenza viruses, raising the risk of reemergence in humans when sufficient susceptible populations arise.IMPORTANCEWe describe the evolutionary origins and antigenic properties of influenza A viruses isolated from two separate Australian swine populations from 2012 to 2016, showing that these viruses are distinct from each other and from those isolated from swine globally. Whole-genome sequencing of virus isolates revealed a high genotypic diversity that had been generated exclusively through the introduction and establishment of human influenza viruses that circulated in past seasons. We detected six reassortants with gene segments derived from human H1N1/H1N1pdm09 and various human H3N2 viruses that circulated during various periods since 1968. We also found that these swine viruses were not related to swine viruses collected elsewhere, indicating independent circulation. The detection of unique lineages and genotypes in Australia suggests that isolated swine populations that are sufficiently large can sustain influenza virus for extensive periods; we show direct evidence of a sustained transmission for at least 4 years between 2012 and 2016.

scholarly journals RNA-Sequencing-Based Transcriptomic Analysis Reveals a Role for Annexin-A1 in Classical and Influenza A Virus-Induced Autophagy

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1399 ◽  
Author(s):  
Jianzhou Cui ◽  
Dhakshayini Morgan ◽  
Dao Han Cheng ◽  
Sok Lin Foo ◽  
Gracemary L. R. Yap ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Infection ◽  
Critical Role ◽  
Mtor Inhibitors ◽  
Influenza Viruses ◽  
Annexin A1 ◽  
Underlying Mechanisms

Influenza viruses have been shown to use autophagy for their survival. However, the proteins and mechanisms involved in the autophagic process triggered by the influenza virus are unclear. Annexin-A1 (ANXA1) is an immunomodulatory protein involved in the regulation of the immune response and Influenza A virus (IAV) replication. In this study, using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 (CRISPR associated protein 9) deletion of ANXA1, combined with the next-generation sequencing, we systematically analyzed the critical role of ANXA1 in IAV infection as well as the detailed processes governing IAV infection, such as macroautophagy. A number of differentially expressed genes were uniquely expressed in influenza A virus-infected A549 parental cells and A549 ∆ANXA1 cells, which were enriched in the immune system and infection-related pathways. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway revealed the role of ANXA1 in autophagy. To validate this, the effect of mechanistic target of rapamycin (mTOR) inhibitors, starvation and influenza infection on autophagy was determined, and our results demonstrate that ANXA1 enhances autophagy induced by conventional autophagy inducers and influenza virus. These results will help us to understand the underlying mechanisms of IAV infection and provide a potential therapeutic target for restricting influenza viral replication and infection.

scholarly journals Double-Edged Role of Interleukin 17A in Streptococcus pneumoniae Pathogenesis During Influenza Virus Coinfection

2019 ◽  
Vol 220 (5) ◽  
pp. 902-912 ◽  
Author(s):  
Ganesh Ambigapathy ◽  
Taylor Schmit ◽  
Ram Kumar Mathur ◽  
Suba Nookala ◽  
Saad Bahri ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Puerto Rico ◽  
Streptococcus Pneumoniae ◽  
Influenza A ◽  
Invasive Disease ◽  
Wild Type ◽  
Interleukin 17A ◽  
Influenza A H1n1 ◽  
Virus Influenza

AbstractBackgroundWe sought to determine the role of host interleukin 17A (IL-17A) response against colonizing Streptococcus pneumoniae, and its transition to a pathogen during coinfection with an influenza virus, influenza A H1N1 A/Puerto Rico/8/1934 (PR8).MethodWild-type (WT) C57BL/6 mice were intranasally inoculated with S. pneumoniae serotype 6A to establish colonization and later infected with the influenza strain, PR8, resulting in invasive S. pneumoniae disease. The role of the IL-17A response in colonization and coinfection was investigated in WT, RoRγt−/− and RAG1−/− mice with antibody-mediated depletion of IL-17A (WT) and CD90 cells (RAG1−/−).ResultsRAG1−/− mice did not clear colonization and IL-17A neutralization impaired 6A clearance in WT mice. RoRγt−/− mice also had reduced clearance. S. pneumoniae–PR8 coinfection elicited a robust IL-17A response in the nasopharynx; IL-17A neutralization reduced S. pneumoniae invasive disease. RoRγt−/− mice also had reduced S. pneumoniae disease in a coinfection model. Depletion of CD90+ cells suppressed the IL-17A response and reduced S. pneumoniae invasion in RAG1−/− mice.ConclusionOur data show that although IL-17A reduces S. pneumoniae colonization, coinfection with influenza virus elicits a robust innate IL-17A response that promotes inflammation and S. pneumoniae disease in the nasopharynx.

Vaccine development for protecting swine against influenza virus

2012 ◽  
Vol 13 (2) ◽  
pp. 181-195 ◽  
Author(s):  
Qi Chen ◽  
Darin Madson ◽  
Cathy L. Miller ◽  
D.L. Hank Harris
Keyword(s):  
Influenza Virus ◽  
Vaccine Development ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Cross Protection ◽  
Antigenic Drift ◽  
Financial Loss ◽  
Heterologous Challenge ◽  
Current Vaccine ◽  
Sea Mammals

AbstractInfluenza virus infects a wide variety of species including humans, pigs, horses, sea mammals and birds. Weight loss caused by influenza infection and/or co-infection with other infectious agents results in significant financial loss in swine herds. The emergence of pandemic H1N1 (A/CA/04/2009/H1N1) and H3N2 variant (H3N2v) viruses, which cause disease in both humans and livestock constitutes a concerning public health threat. Influenza virus contains eight single-stranded, negative-sense RNA genome segments. This genetic structure allows the virus to evolve rapidly by antigenic drift and shift. Antigen-specific antibodies induced by current vaccines provide limited cross protection to heterologous challenge. In pigs, this presents a major obstacle for vaccine development. Different strategies are under development to produce vaccines that provide better cross-protection for swine. Moreover, overriding interfering maternal antibodies is another goal for influenza vaccines in order to permit effective immunization of piglets at an early age. Herein, we present a review of influenza virus infection in swine, including a discussion of current vaccine approaches and techniques used for novel vaccine development.

scholarly journals Role of Sialic Acid Binding Specificity of the 1918 Influenza Virus Hemagglutinin Protein in Virulence and Pathogenesis for Mice

2009 ◽  
Vol 83 (8) ◽  
pp. 3754-3761 ◽  
Author(s):  
Li Qi ◽  
John C. Kash ◽  
Vivien G. Dugan ◽  
Ruixue Wang ◽  
Guozhong Jin ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Sialic Acid ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Binding Specificity ◽  
Influenza Viruses ◽  
Virulence Determinants ◽  
Sialic Acid Binding ◽  
1918 Influenza

ABSTRACT The 1918 influenza pandemic caused more than 40 million deaths and likely resulted from the introduction and adaptation of a novel avian-like virus. Influenza A virus hemagglutinins are important in host switching and virulence. Avian-adapted influenza virus hemagglutinins bind sialic acid receptors linked via α2-3 glycosidic bonds, while human-adapted hemagglutinins bind α2-6 receptors. Sequence analysis of 1918 isolates showed hemagglutinin genes with α2-6 or mixed α2-6/α2-3 binding. To characterize the role of the sialic acid binding specificity of the 1918 hemagglutinin, we evaluated in mice chimeric influenza viruses expressing wild-type and mutant hemagglutinin genes from avian and 1918 strains with differing receptor specificities. Viruses expressing 1918 hemagglutinin possessing either α2-6, α2-3, or α2-3/α2-6 sialic acid specificity were fatal to mice, with similar pathology and cellular tropism. Changing α2-3 to α2-6 binding specificity did not increase the lethality of an avian-adapted hemagglutinin. Thus, the 1918 hemagglutinin contains murine virulence determinants independent of receptor binding specificity.

scholarly journals Protective Role of Combined Polyphenols and Micronutrients against Influenza A Virus and SARS-CoV-2 Infection In Vitro

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1721
Author(s):  
Marta De Angelis ◽  
David Della-Morte ◽  
Gabriele Buttinelli ◽  
Angela Di Martino ◽  
Francesca Pacifici ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Viral Proteins ◽  
Antiviral Effect ◽  
Inhibitory Effect ◽  
Protective Role ◽  
Virus Infections ◽  
Infected Cells ◽  
Respiratory Virus Infections

Polyphenols have been widely studied for their antiviral effect against respiratory virus infections. Among these, resveratrol (RV) has been demonstrated to inhibit influenza virus replication and more recently, it has been tested together with pterostilbene against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present work, we evaluated the antiviral activity of polydatin, an RV precursor, and a mixture of polyphenols and other micronutrients, named A5+, against influenza virus and SARS-CoV-2 infections. To this end, we infected Vero E6 cells and analyzed the replication of both respiratory viruses in terms of viral proteins synthesis and viral titration. We demonstrated that A5+ showed a higher efficacy in inhibiting both influenza virus and SARS-CoV-2 infections compared to polydatin treatment alone. Indeed, post infection treatment significantly decreased viral proteins expression and viral release, probably by interfering with any step of virus replicative cycle. Intriguingly, A5+ treatment strongly reduced IL-6 cytokine production in influenza virus-infected cells, suggesting its potential anti-inflammatory properties during the infection. Overall, these results demonstrate the synergic and innovative antiviral efficacy of A5+ mixture, although further studies are needed to clarify the mechanisms underlying its inhibitory effect.

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