6th International Influenza Meeting

Contribution List

42. A dose-response approach using mixed dose-groups shows immune-potentiating capacity and improved efficacy in ferrets of the cationic liposomal CAF09 adjuvant in an H7N9 influenza whole inactivated virus vaccine challenge study.

Paper presentation

Background
Often contribution of an adjuvant to vaccine efficacy is shown in studies using one or up to three different doses. The suboptimal vaccine dose is determined in a prior dose finding study or based on literature. In either case, reproducibility is a problem, which affects the window to show improvement by the adjuvant. Another limitation is that these studies provide information...

31. A novel negative-strand polarity protein NSP of influenza A virus in infected mice

Oral presentation

Influenza A virus belongs to enveloped viruses with a negative polarity RNA genome consisting of 8 RNA segments, which transcribe a template synthesis of positive-sense mRNAs translating 14 unique viral proteins with splicing and translational shift mechanisms in some mRNAs. Through this classical negative polarity pathway, the 8’th NS segment encodes the anti-interferon NS1 protein (mw 27...

108. Aconitate decarboxylase and itaconic acid reduce inflammation and host susceptibility in influenza A virus infection

Oral presentation

Aconitate decarboxylase 1 (ACOD1) catalyzes the conversion of cis-aconitate to itaconic acid, and its activity is highly regulated in sterile inflammation and host responses to some bacterial pathogens. Very little is known about its role in anti-viral defenses. We have therefore used targeted deletion of ACOD1 in mice and THP-1 cells, as well as exogenous addition of itaconic acid and...

43. Activating proteases of a novel emerging H7N9 influenza A virus

Oral presentation

Activation of the hemagglutinin (HA) of influenza A viruses by host proteases is a prerequisite for infectivity. The HA of low pathogenic avian influenza A (LPAI) H7N9 viruses is cleaved at a single arginine by TMPRSS2. In 2016, the HA of the H7N9 virus mutated into highly pathogenic avian influenza A (HPAI) variants with multiple basic amino acids at the cleavage site. These novel viruses...

53. An Infection-Triggered SUMO Switch Controls Induction of an Antiviral Program by TRIM28

Oral presentation

Dynamic post-translational modification of diverse proteins with SUMO (small ubiquitin-like modifier) is critical to orchestrate cellular recovery from genomic damage, proteotoxic stress and pathogen insult. Using a quantitative affinity proteomics approach, we surveyed the pan-viral host SUMOylation response and identified a spectrum of common and unique SUMO remodelling events that are...

72. Aniline-based inhibitors of influenza H1N1 virus acting on hemagglutinin-mediated fusion

Paper presentation

The influenza virus hemagglutinin (HA) is responsible for fusion between the viral and endosomal membranes during influenza virus entry. This fusion process can be blocked by compounds interfering with the acid-induced conformational change of HA.
After identifying two series of easily accessible anilines as inhibitors of influenza A/H1N1 virus, extensive chemical synthesis and analysis of the...

26. Antigenic properties of the recent human influenza A (H3N2)viruses isolated in MDCK and MDCK-Siat1 cells

Paper presentation

Keywords: influenza, A(H3N2), etiology, virus isolation, antigenic analysis
METHODS: Virus isolation in MDCK and MDCK-Siat1 cells, identification, antigenic analysis in HI(hemagglutination inhibition) and MN (microneutralization) assays with the panel of rat and ferret polyclonal- post-infection antisera,
RESULTS: During the epidemic season 2016-2017 influenza A(H3N2) viruses were dominant...

35. Bispecific Fc gamma receptor engaging molecules directed against the conserved viral M2 ectodomain protect against influenza A virus infections

Oral presentation

Influenza virus infections cause 3 to 5 million cases of severe illness and 250 000 to 500 000 deaths each year. The best way to prevent disease is vaccination. However due to the short immune memory and antigenic drift in the viral hemagglutinin and neuraminidase protein, vaccines need to be administered yearly. Therefore, and as a measure against pandemic influenza outbreaks, antivirals are...

81. Characterization of the entire landscape of peptides presented by MHC during influenza virus infection

Paper presentation

Influenza viruses (IV) infection is a public health concern worldwide. Currently, all available vaccines as well as antiviral drugs that target the virus itself are prone to resistance. Lesson learned from previous pandemic outbreaks is that people with a preexisting cellular immune response are either protected or developed less severe disease against the infection. This observation leads to...

68. Co-circulation of two Yamagata-lineage clades of influenza B viruses during the 2013 and 2014 influenza seasons in Thailand and implication for vaccine effectiveness

Paper presentation

Background: The low vaccine effectiveness (VE) against influenza B-Yamagata lineage viruses in Thailand during the 2013 (25%, 95% confidence interval [CI], -120% to 75%) and 2014 (23%, 95% CI, -236% to 82%) seasons was estimated in a VE study. The WHO recommended influenza B strains in the 2013 and 2014 Southern Hemisphere trivalent vaccine belong to Yamagata clade 3 (2013) and Yamagata clade...

45. Co-infection of influenza A virus and Streptococcus pneumoniae in laboratory mouse

Paper presentation

Influenza viruses are the cause of highly contagious infectious diseases. Their genetic variability allows them to grow every year in human population, emerging to local epidemics, sometimes pandemics. Frequently associated bacterial co-infections are responsible for higher morbidity and mortality rates during the spread of influenza. Bacteria, commonly colonizing the upper respiratory tract...

86. Cross-protective potential and protection-relevant immune mechanisms of whole inactivated influenza virus vaccines are determined by adjuvants and route of immunization

Oral presentation

Adjuvanted whole inactivated virus (WIV) influenza vaccines show promise as universal influenza vaccine candidates. Using WIV as basis we assessed the relative efficacy of different adjuvants by carrying out a head-to-head comparison of the liposome-based adjuvants CAF01 and CAF09 and the protein-based adjuvants CTA1-DD and CTA1-3M2e-DD and evaluated whether one or more of the adjuvants could...

94. Decay accelerating factor as a virulence determinant in influenza A virus infection

Oral presentation

The complement is no longer considered a mere killer of infected cells and pathogens, but is viewed a key player in immunity. It bridges innate and adaptive responses, and orchestrates the intensity of immunological and inflammatory processes by communicating with immune cells. Interactions are beginning to be fully appreciated, and their identification is crucial, as excess complement...

19. Detection and characterisation of influenza virus RNA polymerase dimers using Bimolecular Fluorescence Complementation (BiFC)

Paper presentation

Influenza virus encodes a heterotrimeric RNA-dependent RNA polymerase (RdRP), composed of subunits PB1, PB2 and PA. The RdRP carries out both transcription and replication of the viral RNA genome segments in the context of ribonucleoproteins (RNPs). Replication of negative-sense viral RNA is a two-step process, progressing via a positive-sense complementary RNA intermediate. The mechanism of...

70. Detection of Antiviral Resistance of Influenza Viruses in Bhutan, Nepal, the Philippines, and Thailand during 2013 to 2015

Paper presentation

Background: Influenza virus surveillance in Bhutan, Nepal, the Philippines and Thailand has conducted since 2008. Collected samples were tested by real-time RT-PCR (rRT-PCR) to detect influenza viruses. Antiviral resistance of randomly selected samples was also examined. This study aimed to detect antiviral resistance of samples collected from 2013 to 2015.
Methods: A total of 241...

62. Development and optimization of the assay for screening the compounds inhibiting endonuclease activity and disrupting cap-binding of influenza A polymerase

Paper presentation

Influenza virus A circulates in birds and mammals and causes severe infectious disease with potential fatal outcomes. Virus circulates worldwide and triggers annual epidemics that affect from 3 to 5 million people each year (WHO, 2014). There are two classes of anti-influenza drugs available: neuraminidase and M2 channel inhibitors. Increasing of resistance against these two types of...

91. Endosomal cholesterol accumulation is a host cell-protective mechanism inhibiting endosomal escape of influenza A virus

Oral presentation

With annual epidemics occurring in all parts of the world and the risk of global outbreaks, IAV infections remain a major threat to public health. Infected host cells detect viral components and mount an interferon (IFN)-mediated response to restrict virus propagation and spread of infection. The contribution of endosomal cholesterol levels, especially in the context of the IFN-induced...

111. ERK-phosphorylation, a valuable Biomarker to invest the effectiveness of MEK-inhibitors as Antivirals against Influenza

Paper presentation

The interest is increasing rapidly in the use of biomarkers and surrogate markers as primary measures of the effectiveness of investigational drugs in definitive drug trials. We develop MEK-inhibitors as antivirals against influenza. Here, the status of ERK-phosphorylation represents a perfect surrogate marker of the drug effectiveness.
There are various tools available to detect...

114. ERK-phosphorylation, a valuable Biomarker to invest the effectiveness of MEK-inhibitors as Antivirals against Influenza

Paper presentation

Julia Koch-Heier1,2 and Oliver Planz1,2

1)Atriva Therapeutics GmbH; Tuebingen, Germany
2)Eberhard Karls University, Department of Immunology, Tuebingen, Germany,

The interest is increasing rapidly in the use of biomarkers and surrogate markers as primary measures of the effectiveness of investigational drugs in definitive drug trials. We develop MEK-inhibitors as antivirals against...

58. Establishment of in vitro assays for the potency of the influenza vaccines based on the macrophage activations

Paper presentation

Potency of inactivated influenza vaccines have been measured as a content of hemagglutinin (HA) antigen possessing the biological activities by single radial immunodiffusion (SRID) assay based on antigen–antibody interactions. Although this assay is a golden standard for measuring vaccine potency, it takes long time to prepare appropriate strain-specific reagents. Therefore, we developed a new...

79. Eurasian avian-like swine influenza viruses harbor increased pandemic potential due to MxA escape mutations in their nucleoprotein

Oral presentation

To cross the human species barrier, influenza A viruses (IAV) of avian origin have to overcome the interferon-induced host restriction factor MxA by acquiring distinct mutations in their nucleoprotein (NP). We recently demonstrated that North American classical swine IAV are able to escape MxA restriction partially. Here, we investigated whether the Eurasian avian-like swine IAV lineage...

74. Evaluation of the zoonotic potential of H18N11 virus variant tested in the ferret model

Oral presentation

Influenza A viruses (IAV) are important zoonotic pathogens that cause epidemic outbreaks in birds, swine and other mammals. In 2012 and 2013 two influenza A-like virus genomes were found in little yellow-shouldered fruit bats (Sturnira lilium) in Guatemala and flat-faced fruit bats (Artibeus planirostris) in Peru, provisionally designated as H17N10 and H18N11. Conventional IAV hemagglutinins...

73. Evolution of influenza A virus nucleoprotein is influenced by the E3 ubiquitin ligase activity of the interferon-inducible Tripartite Motif (TRIM)22 protein

Oral presentation

Influenza A virus (IAV) continuously mutates under both intrinsic and immunologically-driven selections. We previously identified TRIM22 protein as a restriction factor of seasonal but not of pandemic (pdm) H1N1 viruses. As TRIM22 restriction is due to a direct interaction with the viral nucleoprotein (NP) leading to its ubiquitination and proteasome degradation, we evaluated the evolution of...

15. Filamentous morphology of recombinant A/WSN/33 (H1N1) virions detected with novel electron microscopy protocols

Paper presentation

Pleiomorphic morphology (spherical, ellipsoidal, filamentous or irregular) of virions is one of the characteristics of Influenza virus. Filamentous phenotype is thought to be favorable for virus transmission in nature. As was shown for several virus strains, it is supported by specific amino acid changes in the matrix M1 protein and might be influenced by some host cellular components. The...

66. Fusion peptides mediate influenza viral fusion via two sequential mechanisms

Oral presentation

Cell entry by influenza virus is mediated by the hemagglutinin protein. Longstanding mutagenesis experiments indicate that, while refolding of hemagglutinin into a coiled-coil structure is required for fusion, intramembrane activity of the fusion peptides is also required. However, the mechanism for this and precisely how fusion peptides act within membranes to drive viral fusion has been...

95. Generation of a human and mouse ex vivo lung culture model for translational studies on respiratory viruses

Paper presentation

Ex vivo lung culture models provide an excellent tool to investigate basic and translational research questions. Here, we have established a human lung culture model using human lung tissue from patients undergoing lung surgery and an analogous mouse ex vivo lung culture model to study important aspects of viral replication, pathogenesis and the cellular antiviral immune response towards...

57. HDACs INHIBITOR TRICHOSTATIN A ENHANCES DISEASE SEVERITY AND LUNG PATHOLOGY IN INFLUENZA A/H3N2-INFECTED MICE

Paper presentation

Histone deacetylases (HDACs) are epigenetic factors modulating gene expression related to numerous biological processes including inflammation. All mechanisms can turn on/off the transcription of genes creating a network of reinforcing or counteracting signals in the cell. Thus, the application of molecules - inhibitors/activators that alter their activity might influence in an unexpected...

39. High virulence of a natural H4N2 avian influenza virus with a polybasic cleavage motif after mutation in the hemagglutinin or reassortment with highly pathogenic H5N1 virus

Oral presentation

According to the definition of the OIE, highly pathogenic (HP) avian influenza viruses (AIVs) are any AIV with an intravenous pathogenicity index (IVPI) ≥1.2, or H5 and H7 viruses with a polybasic cleavage site (CS) in the hemagglutinin (HA). However, according to this definition non-H5/H7 viruses with a polybasic CS, which were rarely reported from nature, are classified as low pathogenic...

48. Homology-based modeling of the C-terminal inner region of pandemic H1N1 Influenza virus hemagglutinin

Paper presentation

Influenza virus hemagglutinin cytoplasmic (intraviral) domain plays crucial role in membrane fusion promotion during virus entry and participates in progeny virions assembly. The structure of this C-terminal region located inside the virion under the viral membrane has not been determined by crystallographic methods yet. The ab-initio PepFOLD 3.5 method of 3D-modeling predicts that the...

18. Host responses to influenza virus infection in the peripheral blood are similar in mice and men

Paper presentation

Influenza virus (IV) infections represent a very serious public health problem. At present, no established biomarkers exist to support diagnosis for respiratory viral infections. Mouse human cross-species comparisons are often compromised by the fact that animal studies concentrate on the infected lungs whereas in humans almost all studies use peripheral blood from patients. In addition, human...

63. How to care for your influenza filaments

Paper presentation

Clinical isolates of influenza virus exhibit a range of morphologies, from spheres with diameters of 120 nm to filaments with lengths sometimes exceeding 30,000 nm. Despite decades of laboratory studies, the functional properties of filaments are still unclear.
Early studies of filaments suggested that they could be damaged by common laboratory manipulations, potentially skewing the results of...

50. IAV-NS1 inhibits global transcription of the host cell and is associated with nuclear Chromatin/DNA

Paper presentation

To study the function of NS1 independent of an IAV infection, we expressed a NS1 estrogen receptor (ERT) fusion-protein that is inducible by tamoxifen. Incubation of NS1ERT expressing cells with tamoxifen at least partially complements the attenuated replication of IAVs lacking NS1 suggesting that a functionally active NS1 is induced. Addition of tamoxifen to cells expressing NS1ERT from...

60. Identification of key kinases required for influenza A virus entry as novel drug targets

Oral presentation

Although annual epidemics of seasonal influenza affect around 10% of the global population, current treatment options are limited and development of new antivirals is urgently needed. Here, we reveal key kinases required for influenza A virus (IAV) entry as potential novel drug targets. Using SILAC-based quantitative phosphoproteomics we quantified over 3000 IAV-induced phosphorylation changes...

21. IFN-λ enhances influenza immunity by stimulating TSLP release during intranasal immunization

Oral presentation

Interferon-λ (IFN-λ) acts on epithelial cells and mediates innate antiviral protection of mucosal surfaces. Here we report that IFN-λ can also enhance adaptive immunity following infection of the respiratory tract. Mice deficient in IFN-λ signaling showed an impaired antibody response after influenza virus infection. We further found that subunit vaccines enriched with IFN-λ induced strongly...

82. Increased pathogenicity in mice of a mouse-adapted influenza H7N9 virus was associated with delayed host innate immune responses

Paper presentation

An avian influenza virus A/Anhui/1/2013 (Anhui; A/H7N9) was adapted in mice (Anhui-M), which showed higher pathogenicity than did the original strain (Anhui-E). Fifty % of lethal doses of each virus were 2.5 x 10⁴ pfu/50 μL (Anhui-E) and 50 pfu/50 μL (Anhui-M), respectively. When mice were inoculated nasally with 4 μl (40xLD₅₀) of each virus, which volume allows...

107. Induction of mannitol metabolism in influenza A virus infected cells

Oral presentation

Influenza A virus (IAV) infection leads to pathogenetically important metabolic changes in host cells, but a comprehensive functional analysis of substrate utilization in IAV-infected cells has not been performed. We adapted the Phenotype MicroArrayTM for mammalian cells system to study changes in host cell respiration during IAV infection, based on simultaneous analysis of metabolism on 367...

103. Infection-induced heterosubtypic immunity against influenza virus correlates better with humoral than cellular immunity in TIV-vaccinated mice and benefits from innate immune activation.

Oral presentation

Conventional influenza vaccines aim at the induction of virus-neutralizing antibodies. However, influenza vaccine efficiencies are often low. We investigated to what extent infection-permissive immunity provided by a seasonal trivalent inactivated influenza virus vaccine (TIV) could modulate disease and virus-induced host responses after infection with H1N1 virus that matches the vaccine. More...

90. Influenza A virus M2 protein interacts with cellular Na,K-ATPase: Does it have a pathophysiological role in influenza pneumonia?

Oral presentation

Influenza A Virus (IAV) infections of the lower respiratory tract can induce viral pneumonia resulting in acute lung injury (ALI/ARDS) with fatal outcome. Characteristics of an IV-induced pneumonia are an alveolar epithelial cell (AEC) damage and accumulation of protein-rich edema fluid in the alveolar compartment impairing gas exchange. Depending on a sodium gradient established by the...

28. Influenza winter 2017/2018 winter season in Umbria (Italy): influenza virus circulation and vaccine immunogenicity

Paper presentation

The 2017/2018 winter season was characterized by a high and persistent influenza virus activity. A co-circulation of A/H3N2, A/H1N1 and B Influenza viruses was observed and their genetic and antigenic characterization induced WHO to recommend the inclusion of new strains of influenza A/H1N1 and B viruses in the 2018/2019 influenza vaccine.
We studied the 2017/2018 influenza virus circulation...

36. Inhibition of RIPK3-dependent cell death as immune antagonism

Oral presentation

The risk of emerging pandemic influenza A viruses (IAV) that approach the devastating 1918 strain motivates finding strain-specific host-pathogen mechanisms. During infection, dendritic cells (DC) mature into antigen-presenting cells that activate T cells, linking innate to adaptive immunity. DC infection with seasonal IAVs, but not with the 1918 and 2009 pandemic strains, induces global RNA...

92. Interferon response is essential in containing human pathogenic Bourbon virus, an influenza-like, tick-borne Orthomyxovirus

Oral presentation

A hitherto unknown viral pathogen was isolated in 2014 from a patient in eastern Kansas who died with high viremia shortly after disease symptoms developed (Kosoy et al., 2015). Additional cases with mild but also fatal outcomes have since occurred in the US. The novel virus, designated Bourbon virus (BRBV), is an influenza-like virus belonging to the genus of tick-borne Thogotoviruses in the...

78. Interferon-beta stimulation by aberrant influenza virus RNAs is sequence dependent

Paper presentation

The influenza A virus (IAV) genome consists of eight segments of negative strand viral RNA (vRNA). These segments are replicated in the nucleus of the host cell by the viral RNA dependent RNA polymerase (RdRp) in the context of nucleoprotein (NP)-coated viral ribonucleoprotein (vRNP) complexes. In addition to making full-length copies of the vRNA segments, the RdRp generates a range of...

75. Interleukin-1β paves the way for protective lung-resident memory T cells: implications for a universal flu vaccine?

Oral presentation

Tissue-resident memory T-cells (TRM) are increasingly recognized as important, cross-reactive immune component in the protection against influenza A viruses (IAV). However, there is a lack of specific vaccine strategies to elicit potent TRM responses. Here, we evaluated vector-encoded IL-1β as genetic adjuvant in intranasal adenoviral vector immunizations against IAV.
First of all, we showed...

105. Intradermal DNA vaccination harboring a combination of conserved HA-peptides eliminates/reduces viral shedding and overcomes maternally derived antibodies.

Oral presentation

Swine influenza viruses (SIVs), though not causing abundant mortality, need to be controlled since swine can act as mixing vessels favoring genome reassortment of diverse influenza viruses. To prevent possible emergences of new influenza virus variants, good vaccination strategies remain crucial. We focused on the use of potential conserved immunogenic hemagglutin peptide (HA-peptide) acting...

59. Kinetic analysis of the influenza A virus HA/NA balance reveals contribution of NA to virus-receptor binding and NA-dependent rolling on receptor-containing surfaces

Oral presentation

Influenza A virus (IAV)-sialic acid (SIA) receptor interactions determine viral fitness and host tropism. The dynamics of binding, determined by a receptor-binding hemagglutinin (HA), a receptor-destroying neuraminidase (NA) and a complex in vivo receptor repertoire, are crucial but poorly understood. Biolayer interferometric analysis revealed virtually irreversible IAV binding to surfaces...

49. Kinetics of the T cell response against influenza A virus is influenced by the site of infection

Paper presentation

Influenza A virus (IAV) infects millions of people each year, resulting in respiratory disease with symptoms ranging from a mild common cold to a severe fatal viral pneumonia. Vaccines may protect against multiple IAV subtypes by targeting conserved intracellular epitopes of IAV. By using ferrets, we can assess how the T cell response against IAV is influenced by the site of induction, which...

27. LC3 punctae in IAV-infected cells do not represent double membrane autophagosomes but endosomes

Oral presentation

Influenza A virus (IAV) infection causes accumulation of the autophagy protein LC3 at intracellular membranes and the plasma membrane. M2 directly interacts with LC3 and enhances its accumulation. However, the proton channel activity of the viral M2 protein is critical for LC3 lipidation. Thus it resembles LC3 lipidation in response to compounds that raise the pH of vesicles. Many pathogens...

37. Manipulation of cellular lipid balance as a potent antiviral target for enveloped viruses

Oral presentation

The release of viral genome into the host cytoplasm and its translocation to the nucleus is strongly dependent on the fusion of Influenza A virus (IAV) envelope with host endosomal membranes. Recent publications have already delineated the importance of cellular cholesterol levels on the infectivity of IAV, as interferons (IFN) are also impairing cholesterol levels and its cellular...

34. Molecular Anatomy of an Influenza Virion

Oral presentation

Influenza virions are complex and vary in their shape and composition. As a result, no single method can describe them in detail. We therefore applied a multidisciplinary approach, generating a highly detailed model of an average influenza virion that provided a basis for assessing natural variation.

By combining cryo-electron tomography, proteomics, lipidomics and molecular modelling, we...

44. Monitoring of influenza: Whole-Genome Sequencing to provide insights into disease severity

Paper presentation

Laura Van Poelvoorde 1, 2, 3, 4, Sigrid C.J. De Keersmaecker 1, Kevin Vanneste 1, Raf Winand 1, Qiang Fu 1, Steven Van Gucht 2, Isabelle Thomas 2 , Xavier Saelens 3,4, Cyril Barbezange 2, Nancy Roosens 1

1 Transversal & Applied Genomics, Sciensano, Brussels, Belgium; 2 Viral diseases, Sciensano, Brussels, Belgium; 3 VIB Center for Medical Biotechnology Center, VIB, Ghent, Belgium; 4...

47. Mutational analysis of the M2 ion channel proteins of avian and bat influenza A viruses

Oral presentation

The matrix protein 2 (M2) is a multifunctional protein, which plays a crucial role in influenza A virus entry and egress. In this study, we investigated the role of M2 protein in the context of a glycoprotein (G)-deficient vesicular stomatitis virus (VSV∆G) encoding the three envelope proteins hemagglutinin (HA), neuraminidase (NA) and M2 of A/chicken/Rostock/8/34 (H7N1), a highly pathogenic...

38. Mutations in conserved NA residues of H5N1 naturally isolated from humans modulated sialidase activity and virulence in mice but not in chickens

Oral presentation

HPAIV H5N1 of clade 2.2.1 is endemic in Egypt since 2006 and 2 distinct clades have evolved: clade 2.2.1.1 in commercial poultry and clades 2.2.1.2 and 2.2.1.2a in humans and poultry. Compared to the neuraminidase (NA) of the parental 2.2.1 viruses, avian viruses in clade 2.2.1.1 possessed one mutation (I168T) and human-like viruses in clades 2.2.1.2 and 2.2.1.2a had 4 mutations (A46D, L204M,...

71. MX1 requirements for influenza A virus restriction

Paper presentation

Type 1 interferons (IFNs) are produced by infected cells upon detection of pathogenic agents and are the first line of defence against viral infections. IFNs induce the expression of hundreds of IFN-stimulated genes (ISGs), both in infected and neighbouring cells. The products of these ISGs in turn induce in cells a potent antiviral state, capable of limiting viral replication. The...

98. Oncolytic influenza virus infection restores immunocompetence of lung tumor-associated alveolar macrophages

Oral presentation

The majority of all lung cancers belong to the subtype of non-small-cell lung carcinomas (NSCLCs), which are known to be insensitive to chemotherapy and radiation. Non-small-cell lung cancer is the most frequent type of lung cancer and demonstrates high resistance to radiation and chemotherapy. Additionally, these tumors develop a highly immunosuppressive tumor-microenvironment as an immune...

76. Overcoming the resistance to influenza A virus infections in mice carrying a deletion in the host protease TMPRSS2 by exchange of amino acids in the hemagglutinin

Paper presentation

Background:
Annual epidemics and occasional pandemics by influenza A virus (IAV) pose a severe threat to human health. Host cell factors that are required for viral spread but not for cellular survival represent ideal targets for anti-viral therapies. The cleavage activation of the influenza virus hemagglutinin (HA) by host cell proteases is essential for viral infectivity. Thus, host...

109. PD0184264, an active metabolite of the MEK-inhibitor CI-1040 shows superior pharmacokinetics and antiviral activity against influenza virus

Paper presentation

Drugs directed against influenza virus directly show the tendency to induce resistance. We have previously shown that influenza virus (IV) highjack cellular factors for its own purpose and that the nuclear RNP export is strongly dependent on the virus-induced activation of the Raf/MEK/ERK signal pathway. Thus, this pathway is most favorable for antiviral intervention, because it is required by...

112. PD0184264, an active metabolite of the MEK-inhibitor CI-1040 shows superior pharmacokinetics and antiviral activity against influenza virus

Paper presentation

Drugs directed against influenza virus directly show the tendency to induce resistance. We have previously shown that influenza virus (IV) highjack cellular factors for its own purpose and that the nuclear RNP export is strongly dependent on the virus-induced activation of the Raf/MEK/ERK signal pathway. Thus, this pathway is most favorable for antiviral intervention, because it is required by...

102. Phenotypic and genotypic analysis of influenza viruses susceptibility to antivirals during the 2017-2018 epidemic season in Russian Federation.

Paper presentation

Being constantly evolving influenza viruses can develop the resistance to the most common used antivirals, such as neuraminidase inhibitors. In this study we show the results of phenotypic and genotypic analysis of influenza A and B viruses isolated in the 2017-2018 season in Russia susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir and M2 proton channel inhibitor...

96. Phosphorylation of serine 205 of influenza A virus NS1 protein as determinant of adaptation and functional evolution

Oral presentation

Influenza A virus (IAV) infections are still a major burden of mankind. High evolution rates as well as the ability to infect a wide range of hosts leads to seasonal epidemics and occasional pandemics. IAV non-structural protein 1 (NS1) is a multi-functional protein that plays diverse roles during virus replication and has been linked to host adaptation. Currently circulating H1N1 viruses in...

55. Phosphorylation of TRIM28 enhances the expression of IFN‐β and proinflammatory cytokines during HPAIV infection of human lung epithelial cells.

Oral presentation

Human infection with highly pathogenic avian influenza viruses (HPAIV) is often associated with severe tissue damage due to hyperinduction of interferons and proinflammatory cytokines. The reasons for this excessive cytokine expression are still incompletely understood, which has hampered the development of efficient immunomodulatory treatment options. The host protein TRIM28 associates to the...

101. Phosphorylation of tyrosine 132 of influenza A virus matrix protein 1 is essential for efficient viral genome packaging and particle assembly

Oral presentation

Rapid development of resistance of influenza A viruses (IAV) to currently available drugs emphasizes the urgent need for novel therapeutics. The highly conserved matrix protein 1 (M1) is a master regulator of the virus life cycle and its multifunctionality is most likely regulated by posttranslational modifications. Phosphorylation of M1 tyrosine 132 (Y132) was previously suggested to be...

69. Phylogenetic analysis of influenza viruses in Bhutan during 2008-2017

Paper presentation

Background: Bhutan does not currently have an influenza vaccination program. Human influenza surveillance has conducted in Bhutan since 2008. Collected samples were tested by real-time RT-PCR (rRT-PCR) to detect and identify influenza viruses. This study aimed to examine the similarity between circulating influenza viruses in Bhutan and the annual vaccine strains through phylogenetic...

64. Phylogenetic analysis of influenza viruses of the seasons 2016-2018 in Ukraine

Paper presentation

Background
The phylogenetic analyses of influenza viruses allow to performing the comparison between viruses and monitoring the evolution in a frame of territory. Influenza viruses have high level of mutations caused by errors of polymerase.
The aim of our work was to analyze variability of influenza viruses type B which were isolated during 2016-2018 years and to construct of phylogenetic...

85. Postnatal priming of interferon and metabolic response programs determines the host’s responsivity to influenza infections later in life

Oral presentation

The morbidity and mortality of newborn infants from influenza infections is low compared to older children and adults. It is largely unclear what reprogramming of immunity causes the higher susceptibility to severe influenza infections with increasing age.
We challenged human respiratory and innate immune cells from healthy newborns and adults with the H1N1/California/04/2009 virus. Next to...

67. Predominant of influenza A (H3N2) clade 3C.2a may have contributed to the low vaccine effectiveness against influenza A (H3N2) in the 2014 influenza season in Thailand

Paper presentation

Abstract

Background: The vaccine effectiveness (VE) against influenza A (H3N2) viruses [A(H3N2)] estimated from a VE study in Thailand was 73% (95% confidence interval [CI], -14% to 94%) and 6% (95% CI, -103% to 56%) in 2013 and 2014 seasons, respectively, when the given A (H3N2) vaccine strain belong to clade 3C.1.
Methods: A total of 15 A (H3N2) viruses from the referred VE study was used...

97. Prodrugs of the Phosphoribosylated Forms of Hydroxypyrazinecarboxamide Pseudobase T-705 and its De-Fluoro-Analogue T-1105 as Potent Influenza Virus Inhibitors

Oral presentation

The nucleobase analogue T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide; favipiravir) is a unique antiviral drug possessing broad anti-RNA virus activity and a high barrier for resistance. When we compared the influenza virus inhibition by T-705 and its non-fluorinated analogue T-1105, the latter proved to be four-fold more potent in Madin-Darby canine kidney (MDCK) cells. In an enzymatic RNA...

14. Prolonged evolution of virus-specific memory T cell immunity post severe avian influenza A (H7N9) virus infection

Oral presentation

Since 2013, influenza A/H7N9 has emerged as the commonest avian influenza subtype causing human infection, and is associated with a high fatality risk. However, the characteristics of immune memory in patients who have recovered from H7N9 infection are not well understood. We assembled a cohort of forty-five H7N9 survivors and followed for up to 15 months after infection. Humoral and cellular...

29. Reassortment of internal protein-encoding gene segments of Eurasian H9N2-type avian influenza A virus (IAV) with co-circulating highly pathogenic H5N1- and H5N8-type IAV strains: Impact on viral replication and pathogenicity in mammalian systems in vitro and in vivo

Oral presentation

Humans are susceptible to infection with influenza A, B and C viruses. Influenza A viruses (IAV) represent worldwide circulating pathogens that cause annual epidemics and occasionally worldwide pandemics, infecting millions of people. In parallel, several high pathogenic avian influenza viruses (HPAIV) and low pathogenic avian influenza viruses (LPAIV) have (occasionally) crossed the species...

99. Replication of bat chimeric influenza viruses is efficiently inhibited by human MxA

Oral presentation

The interferon-induced and antivirally active human GTPase MxA represents a major interspecies-barrier for influenza A viruses (IAVs) of avian origin that has to be overcome in order to establish a new lineage in the human population. As a consequence, all human-adapted IAVs, including the pandemic 1918 and the pH1N1 virus as well as all their descendants, encode adaptive mutations in their...

80. Risk assessment of fifth-wave H7N9 influenza A viruses in mammalian models

Oral presentation

The fifth-wave of the H7N9 influenza epidemic in China was distinguished by a sudden increase in human infections, an extended geographic distribution, and the emergence of highly pathogenic avian influenza (HPAI) viruses. Genetically, some H7N9 viruses from the fifth-wave have acquired novel amino acid changes at positions involved in mammalian adaptation, antigenicity, and HA cleavability....

115. SENSITIVITY OF 2015 KAZAKHSTAN INFLUENZA VIRUSES TO СHEMOTHERAPY DRUGS

Paper presentation

N.G. Klivleyeva, G.V. Lukmanova, T.I. Glebova, N.S. Ongarbayeva, N.T. Saktaganov, M.G. Shamenova, M.K. Kalkozhayeva, S.B. Baiseiit, A.M. Baimukhametova

Institute of Microbiology and Virology, Almaty, Kazakstan

One of the most important characteristics of influenza viruses is resistance to specific medicines. Practice shows that it is impossible to select an etiotropic antiviral drug...

56. Single domain antibodies to probe the antiviral function of interferon-induced MX1 proteins

Paper presentation

For centuries, our immune system has been trapped in an evolutionary arms race with viruses. This relationship has shaped our immune defenses and led to the evolution of several specialized anti-viral proteins. An example of these are the Mx proteins: large GTPases that are part of the antiviral response induced by type I and III interferons, and thus belong to the first line of defense...

40. Species comparisons identify avian ANP32A splice variants that differentially impact influenza A virus polymerase host restriction

Oral presentation

The viral RNA polymerase complex (vPol), comprising PB1, PB2 and PA, is essential for influenza A virus (IAV) replication. Cellular co-factors are necessary for vPol function, and host differences in these proteins act as barriers that limit IAV emergence into new species. ANP32A is a key host determinant of vPol efficiency that likely drives selection of mammalian-adaptive virulence motifs,...

17. Staphylococcus aureus and influenza virus: interaction of pathogens requires interplay of cells via alveolus-on-a-chip model

Oral presentation

Background and objectives
Postinfluenza models of Staphylococcus aureus pneumonia demonstrate the severe outcome of a coinfection associated with substantial morbidity and mortality for patients. To date, investigations concerning microbial infections of the lung are usually carried out in animal models. However, lung anatomy and physiology as well as composition of the immune system differ...

88. Suspected spillover of A/H1N1 (2009) from humans to swine in Ghana: Current status of molecular surveillance

Paper presentation

The emergence of the A/H1N1 (2009) human pandemic influenza virus that had its origin in pigs caused the most influenza pandemic. This has refocused the world’s attention on the possible emergence of zoonotic influenza viruses from pigs. While the human population is in the post-pandemic era with A/H1N1 (2009) now being an endemic seasonal influenza virus, the virus, then referred to as...

54. The 2nd sialic acid-binding site of influenza A virus neuraminidase contributes to the hemagglutinin-neuraminidase-receptor balance

Oral presentation

It is generally accepted that the catalytic activity of influenza A virus (IAV) neuraminidase (NA) needs to match the receptor-binding activity of the corresponding hemagglutinin (HA) and the sialic acid (SIA)-receptor repertoire of the host. What this HA-NA-receptor balance entails at the molecular level is, however, not known. NA of avian, but not human viruses contain a 2nd SIA-binding site...

52. The balance between intrinsic cellular innate, host innate and host adaptive immune responses matters for the outcome of influenza virus respiratory infection

Oral presentation

After lung infection, influenza A viruses (IAVs) have to overcome at least three highly efficient immune defense barriers: the intrinsic cellular innate response, the host innate immune response and the host adaptive immune response. To circumvent these immune defense barriers and propagate successfully, influenza A virus proteins enter into a symbiosis with cellular proteins, altering host...

51. The critical role of hemagglutinin (HA) in transmission of duck-origin H5Nx low-pathogenic avian influenza viruses in chickens

Oral presentation

In wild waterfowl avian influenza viruses (AIV) primarily replicate in the gastrointestinal tract and are shed into the environment at large quantities facilitating transmission to domestic poultry. Continuous circulation of H5 and H7 AIVs in domestic poultry may favour the evolution of highly pathogenic AIVs (HPAIV). To understand the adaptation process of AIV in poultry, we experimentally...

110. The flavonoid Tiliroside demonstrates antiviral potential against influenzavirus by interfering with the viral entry into the host cell

Paper presentation

Viral infections, such as influenza, are a major cause of respiratory disease worldwide with high morbidity/mortality and enormous costs. Because influenza vaccination success is not always present and less than 25% of the population is effectively protected by influenza vaccine, antiviral therapy is an essential tool for controlling influenza viral infection. At present, specific and licensed...

113. The flavonoid Tiliroside demonstrates antiviral potential against influenzavirus by interfering with the viral entry into the host cell

Paper presentation

Xinran Zhang1, Martin Laure1,2, Sascha Rohn3 and Oliver Planz1,2

1)Eberhard Karls University, Department of Immunology, Tuebingen, Germany
2)Atriva Therapeutics GmbH; Tuebingen, Germany
3)Hamburg University, Department of Chemistry, Hamburg, Germany

Viral infections, such as influenza, are a major cause of respiratory disease worldwide with high morbidity/mortality and enormous costs....

30. The HA cleavage is necessary for the M2 channel activation in influenza A virus

Oral presentation

Non-infectious influenza A virus possessing uncleaved HA0 is activated by trypsin via the HA0→HA1/2 cleavage. The cleaved HA1/2 provides virus entry into target cell where the intravirion acidification through the M2 channel plays important role. We have suggested that HA0 plugs the M2 channel and its cleavage into HA1+HA2 by trypsin is responsible for a functional priming of M2 channel...

61. The role of F(ab)2 and Fc fragments of HA2-specific antibodies in the recovery from influenza infection

Paper presentation

Antibodies (Ab) are crucial molecules in the protection of organism against influenza infection. Nowadays, elicitation of cross-protective antibodies targeting the HA stalk domain becomes a promising approach to develop a universal vaccine. Besides virus neutralizing (VN) Abs, the broadly reactive non-neutralizing antibodies contribute to elimination of virus and recovery from influenza...

93. The role of F(ab)2 and Fc fragments of HA2-specific antibodies in the recovery from influenza infection

Paper presentation

Antibodies (Ab) are crucial molecules in the protection of organism against influenza infection. Nowadays, elicitation of cross-protective antibodies targeting the HA stalk domain becomes a promising approach to develop a universal vaccine. Besides virus neutralizing (VN) Abs, the broadly reactive non-neutralizing antibodies contribute to elimination of virus and recovery from influenza...

25. The stalk domain of influenza pH1 HA tolerates substitutions that may confer decreased susceptibility to broadly neutralizing antibodies.

Oral presentation

The highly-conserved influenza hemagglutinin stalk domain is a favoured target for broadly neutralising antibodies (bnAbs), which are heralded as a new class of therapeutic biologics that would inhibit many different strains and subtypes of influenza A viruses. Based on structural and bioinformatics analyses of multiple bnAb-HA co-crystal structures, we rationally designed influenza virus...

84. The Structure of the Influenza A Virus Genome

Oral presentation

The IAV genome consists of eight single-stranded viral RNA (vRNA) segments contained in separate viral ribonucleoprotein complexes (vRNPs) that are packaged together into a single virus particle. The structure of the vRNA is believed to play a role in assembling the different vRNPs into budding virions and in directing reassortment between established human influenza viruses and influenza...

41. TMPRSS2 is the major HA-activating protease for IAV, but not for IBV in the human respiratory tract

Oral presentation

Cleavage of influenza A virus (IAV) and influenza B virus (IBV) hemagglutinin (HA) activation by host proteases is essential for virus infectivity.
The HA of most influenza viruses including seasonal H1N1, H3N2 and IBV as well as the zoonotic-H7N9 virus is cleaved at a single arginine residue by trypsin-like proteases. We identified TMPRSS2 as a protease present in the human airways that...

33. TRIM 25 nuclear translocation is hampered by localisation to influenza A virus non-structural protein 1 cytosolic aggregates

Oral presentation

Recently, research efforts focus on the role of viral RNA species in the context of host antiviral signalling inhibition. Imaging studies give invaluable insights into complex RNA-protein and protein-protein interactions visualized directly at their side of action.
Among the IAV proteins the non-structural protein 1 (NS1) of influenza A virus (IAV) is described to be involved in manifold...

106. Trivalent Live Attenuated Influenza Vaccine (LAIV3) Induces multifaceted antibody response against H1N1 in children

Oral presentation

Influenza is a major respiratory pathogen and vaccination is the main method of prophylaxis. In 2012, the trivalent live attenuated influenza vaccine (LAIV3) was licensed in Europe for use in children. Vaccine-induced antibodies directed against the main viral surface glycoproteins, haemagglutinin (HA) and neuraminidase (NA), play an important role in limiting virus infection. Antibodies to...

46. Trypsin-like serine proteases in the lower respiratory tract of mice and their putative role in proteolytic activation of influenza A and B viruses

Oral presentation

Cleavage of the hemagglutinin (HA) precursor protein into its subdomains by host cell proteases is essential for virus infectivity, spread and pathogenicity. Seasonal influenza A and B viruses possess a monobasic HA cleavage site with a single arginine and are activated by trypsin-like proteases. TMPRSS2, a type II transmembrane serine protease (TTSP), activates HA with monobasic cleavage site...

65. Tubulin-dependent apical transport of cellular NKA induced by influenza A virus infection.

Paper presentation

Influenza A virus (IAV) infection may cause life-threatening conditions such as “Acute Lung Injury” (ALI) and “Acute Respiratory Distress Syndrome” (ARDS) characterized by lung edema formation, impaired gas exchange leading to death. Clearance of alveolar fluid is strongly dependent on active transport of sodium across alveolar epithelial cells. One of the main ion channels that establish an...

83. Tyrosine kinase 2 is not required for interferon-λ mediated signaling and protection against lethal Influenza A virus infection in mice

Oral presentation

Binding of interferons (IFN) to their respective surface receptors activates JAK kinases such as JAK1, JAK2 and TYK2. Upon activation these kinases mediate the phosphorylation of STAT molecules, which eventually promotes the expression of a large number of IFN-stimulated genes (ISGs) encoding antiviral resistance factors. TYK2 is associated with both the IFNAR1 and the IL-10Rβ receptor chain,...

77. Understanding influenza filament formation through multi-modal imaging strategies

Paper presentation

Wild type influenza A viruses (IAVs) typically form a pleomorphic population of viral particles, ranging from filaments that can be several microns in length to 0.1 micron diameter spheres. However, spherical particles predominate in laboratory-adapted strains, filamentous particles are present in a high proportion of clinical isolates. Despite the wealth of knowledge about the virus life...

89. Viral activation of the Raf/MEK/ERK kinase cascade promotes nuclear export of viral ribonucleoproteins (RNPs) by regulating matrix protein binding to the RNPs

Oral presentation

It was already shown that viral infection leads to the activation of a variety of signaling processes in the infected cells. Some of these activities are necessary for an efficient viral replication. The dependence of the Influenza A virus (IAV) on cellular signaling pathways leads to the opportunity of a novel antiviral strategy by targeting host factors that are essential for viral...

87. Visualizing influenza and parainfluenza virus infection non-invasively in living mice with non-attenuated reporter viruses

Oral presentation

Infection has classically been measured by titering infectious virus recovered from euthanized animals or respiratory washes. In contrast, bioluminescence imaging measures in living animals the expression of luciferase, a marker for the extent of infected cells. It is a powerful tool for studying virus-host interactions yet luciferase insertions attenuate replication and virulence. Propagating...

104. vRNAsite: Prediction and evaluation of viral RNA-RNA interaction sites between influenza A wild type and mutant vRNAs

Paper presentation

Seasonal influenza A virus (IAV) epidemics are difficult to counter with vaccination. This is due to the unique packaging of the eight viral RNA (vRNA) segments and the ability to create reassortants between different strains. One theory about packaging involves vRNA-vRNA interactions (RRI) between different segments [1,2], however to our knowledge there has been no attempt to computationally...

100. Whole-genome characterization of influenza A viruses circulated in Russian Federation in 2015-2018 epidemic seasons

Paper presentation

BACKGROUND: Implementation of NGS technology in the framework of influenza surveillance in Russia significantly improved identification of possible factors that could influence the course of epidemics and the impact of internal genes evolution on pathogenicity and transmission of influenza viruses. Whole-genome sequencing of influenza A viruses selected by the epidemic periods and geography...