Influenza virus neuraminidase contributes to the dextran sulfate-dependent suppressive replication of some influenza A virus strains

ABSTRACT We sequenced the eight segments of influenza A virus strains A/equine/Ibaraki/1/2007 and A/equine/Yokohama/aq13/2010, which are strains of the Florida sublineage clades 1 and 2 of the H3N8 subtype equine influenza virus. These strains have been used as vaccine strains in Japan since 2016 in accordance with World Organization for Animal Health (OIE) recommendations.

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Immunomic Analysis of the Repertoire of T-Cell Specificities for Influenza A Virus in Humans

Journal of Virology ◽

10.1128/jvi.01563-08 ◽

2008 ◽

Vol 82 (24) ◽

pp. 12241-12251 ◽

Cited By ~ 135

Author(s):

Erika Assarsson ◽

Huynh-Hoa Bui ◽

John Sidney ◽

Qing Zhang ◽

Jean Glenn ◽

...

Keyword(s):

Influenza Virus ◽

T Cell ◽

Influenza A Virus ◽

Influenza A ◽

T Cell Responses ◽

Class Ii ◽

Influenza Viruses ◽

Class I ◽

Cell Responses ◽

Virus Strains

ABSTRACT Continuing antigenic drift allows influenza viruses to escape antibody-mediated recognition, and as a consequence, the vaccine currently in use needs to be altered annually. Highly conserved epitopes recognized by effector T cells may represent an alternative approach for the generation of a more universal influenza virus vaccine. Relatively few highly conserved epitopes are currently known in humans, and relatively few epitopes have been identified from proteins other than hemagglutinin and nucleoprotein. This prompted us to perform a study aimed at identifying a set of human T-cell epitopes that would provide broad coverage against different virus strains and subtypes. To provide coverage across different ethnicities, seven different HLA supertypes were considered. More than 4,000 peptides were selected from a panel of 23 influenza A virus strains based on predicted high-affinity binding to HLA class I or class II and high conservancy levels. Peripheral blood mononuclear cells from 44 healthy human blood donors were tested for reactivity against HLA-matched peptides by using gamma interferon enzyme-linked immunospot assays. Interestingly, we found that PB1 was the major target for both CD4+ and CD8+ T-cell responses. The 54 nonredundant epitopes (38 class I and 16 class II) identified herein provided high coverage among different ethnicities, were conserved in the majority of the strains analyzed, and were consistently recognized in multiple individuals. These results enable further functional studies of T-cell responses during influenza virus infection and provide a potential base for the development of a universal influenza vaccine.

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Key amino acid residues of neuraminidase involved in influenza A virus entry

Pathogens and Disease ◽

10.1093/femspd/ftz063 ◽

2019 ◽

Vol 77 (6) ◽

Author(s):

Fangzhao Chen ◽

Teng Liu ◽

Jiagui Xu ◽

Yingna Huang ◽

Shuwen Liu ◽

...

Keyword(s):

Influenza Virus ◽

Amino Acid ◽

Influenza A Virus ◽

Viral Entry ◽

Influenza A ◽

Mutational Analysis ◽

Critical Role ◽

Target Cells ◽

Amino Acid Residues ◽

Influenza Virus Neuraminidase

ABSTRACT Generally, influenza virus neuraminidase (NA) plays a critical role in the release stage of influenza virus. Recently, it has been found that NA may promote influenza virus to access the target cells. However, the mechanism remain unclear. Here, we reported that peramivir indeed possessed anti-influenza A virus (IAV) activity in the stage of viral entry. Importantly, we verified the critical residues of influenza NA involved in the viral entry. As a result, peramivir as an efficient NA inhibitor could suppress the initiation of IAV infection. Furthermore, mutational analysis showed NA might be associated with viral entry via amino acids residues R118, E119, D151, R152, W178, I222, E227, E276, R292 and R371. Our results demonstrated NA must contain the key amino acid residues can involve in IAV entry.

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The Effect of a Lipopolysaccharide from Rhodobacter capsulatus PG on Inflammation Caused by Various Influenza Strains

Acta Naturae ◽

10.32607/20758251-2019-11-3-46-55 ◽

2019 ◽

Vol 11 (3) ◽

pp. 46-55

Author(s):

S. V. Zubova ◽

M. F. Vorovich ◽

A. S. Gambaryan ◽

A. A. Ishmukhametov ◽

S. V. Grachev ◽

...

Keyword(s):

Body Weight ◽

Influenza Virus ◽

Blood Serum ◽

Influenza A Virus ◽

Inflammatory Cytokines ◽

Influenza A ◽

Rhodobacter Capsulatus ◽

Igg Antibodies ◽

Anti Inflammatory ◽

Virus Strains

The development of a specific inflammation in mice that had been infected by two influenza virus strains, A/chicken/Kurgan/5/2005 (H5N1) and A/Hamburg/2009 MA (H1N1), was studied. We investigated the effect of a non-toxic lipopolysaccharide from Rhodobacter capsulatus PG on the survival and body weight of the mice, production of IgG antibodies, and the induction of pro- and anti-inflammatory cytokines in blood serum. The administration of the R. capsulatus PG lipopolysaccharide was shown to induce interferon- synthesis, both in healthy and influenza A virus-infected mice, and to promote production of antiviral antibodies in the blood of the influenza-infected animals.

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Combinatory Treatment with Oseltamivir and Itraconazole Targeting Both Virus and Host Factors in Influenza A Virus Infection

Viruses ◽

10.3390/v12070703 ◽

2020 ◽

Vol 12 (7) ◽

pp. 703 ◽

Cited By ~ 3

Author(s):

Sebastian Schloer ◽

Jonas Goretzko ◽

Stephan Pleschka ◽

Stephan Ludwig ◽

Ursula Rescher

Keyword(s):

Influenza Virus ◽

Influenza A Virus ◽

Influenza A ◽

Interaction Analysis ◽

Treatment Success ◽

Combined Treatment ◽

Antiviral Effect ◽

Neuraminidase Inhibitor ◽

Oseltamivir Resistance ◽

Virus Strains

Influenza virus infections and their associated morbidity and mortality are a major threat to global health. Vaccination is an effective influenza prevention measure; however, the effectiveness is challenged by the rapid changes in the influenza virus genome leading to viral adaptation. Emerging viral resistance to the neuraminidase inhibitor oseltamivir limits the treatment of acute influenza infections. Targeting influenza virus-host interactions is a new and emerging field, and therapies based on the combination of virus- and host-directed drugs might significantly improve treatment success. We therefore assessed the combined treatment with oseltamivir and the repurposed antifungal drug itraconazole on infection of polarized broncho-epithelial Calu-3 cells with pdm09 or Panama influenza A virus strains. We detected significantly stronger antiviral activities in the combined treatment compared to monotherapy with oseltamivir, permitting lower concentrations of the drug than required for the single treatments. Bliss independence drug interaction analysis indicated that both drugs acted independently of each other. The additional antiviral effect of itraconazole might safeguard patients infected with influenza virus strains with heightened oseltamivir resistance.

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Triple Combination of Oseltamivir, Amantadine, and Ribavirin Displays Synergistic Activity against Multiple Influenza Virus Strains In Vitro

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00476-09 ◽

2009 ◽

Vol 53 (10) ◽

pp. 4115-4126 ◽

Cited By ~ 78

Author(s):

Jack T. Nguyen ◽

Justin D. Hoopes ◽

Donald F. Smee ◽

Mark N. Prichard ◽

Elizabeth M. Driebe ◽

...

Keyword(s):

Influenza Virus ◽

Influenza A Virus ◽

Influenza A ◽

New Caledonia ◽

Mdck Cells ◽

The United States ◽

Health Concern ◽

Synergistic Activity ◽

Triple Combination ◽

Virus Strains

ABSTRACT The recurring emergence of influenza virus strains that are resistant to available antiviral medications has become a global health concern, especially in light of the potential for a new influenza virus pandemic. Currently, virtually all circulating strains of influenza A virus in the United States are resistant to either of the two major classes of anti-influenza drugs (adamantanes and neuraminidase inhibitors). Thus, new therapeutic approaches that can be rapidly deployed and that will address the issue of recurring resistance should be developed. We have tested double and triple combinations of the approved anti-influenza drugs oseltamivir and amantadine together with ribavirin against three influenza virus strains using cytopathic effect inhibition assays in MDCK cells. We selected A/New Caledonia/20/99 (H1N1) and A/Sydney/05/97 (H3N2) as representatives of the wild-type versions of the predominant circulating seasonal influenza virus strains and A/Duck/MN/1525/81 (H5N1) as a representative of avian influenza virus strains. Dose-response curves were generated for all drug combinations, and the degree of drug interaction was quantified using a model that calculates the synergy (or antagonism) between the drugs in double and triple combinations. This report demonstrates that a triple combination of antivirals was highly synergistic against influenza A virus. Importantly, the synergy of the triple combination was 2- to 13-fold greater than the synergy of any double combination depending on the influenza virus subtype. These data support the investigation of a novel combination of oseltamivir, amantadine, and ribavirin as an effective treatment for both seasonal and pandemic influenza virus, allowing the efficient use of the existing drug supplies.

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Analysis of the Receptor Specificity of Influenza A Virus Strains Using the Method of Surface Plasmon Resonance

BIOPHYSICS ◽

10.1134/s0006350920020153 ◽

2020 ◽

Vol 65 (2) ◽

pp. 222-224

Author(s):

G. S. Onkhonova ◽

P. Yu. Torzhkova ◽

V. Yu. Marchenko ◽

S. V. Svyatchenko ◽

A. S. Gudymo ◽

...

Keyword(s):

Surface Plasmon Resonance ◽

Influenza A Virus ◽

Surface Plasmon ◽

Plasmon Resonance ◽

Influenza A ◽

Receptor Specificity ◽

Virus Strains

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Influenza A Virus Hemagglutinin and Other Pathogen Glycoprotein Interactions with NK Cell Natural Cytotoxicity Receptors NKp46, NKp44, and NKp30

Viruses ◽

10.3390/v13020156 ◽

2021 ◽

Vol 13 (2) ◽

pp. 156

Author(s):

Jasmina M. Luczo ◽

Sydney L. Ronzulli ◽

Stephen M. Tompkins

Keyword(s):

Influenza Virus ◽

Nk Cells ◽

Influenza A Virus ◽

Influenza A ◽

Nk Cell ◽

Influenza Virus Infection ◽

Target Cells ◽

Natural Cytotoxicity ◽

Activating Receptors ◽

Natural Cytotoxicity Receptors

Natural killer (NK) cells are part of the innate immunity repertoire, and function in the recognition and destruction of tumorigenic and pathogen-infected cells. Engagement of NK cell activating receptors can lead to functional activation of NK cells, resulting in lysis of target cells. NK cell activating receptors specific for non-major histocompatibility complex ligands are NKp46, NKp44, NKp30, NKG2D, and CD16 (also known as FcγRIII). The natural cytotoxicity receptors (NCRs), NKp46, NKp44, and NKp30, have been implicated in functional activation of NK cells following influenza virus infection via binding with influenza virus hemagglutinin (HA). In this review we describe NK cell and influenza A virus biology, and the interactions of influenza A virus HA and other pathogen lectins with NK cell natural cytotoxicity receptors (NCRs). We review concepts which intersect viral immunology, traditional virology and glycobiology to provide insights into the interactions between influenza virus HA and the NCRs. Furthermore, we provide expert opinion on future directions that would provide insights into currently unanswered questions.

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Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

Viruses ◽

10.3390/v13020234 ◽

2021 ◽

Vol 13 (2) ◽

pp. 234

Author(s):

Sarah Al-Beltagi ◽

Cristian Alexandru Preda ◽

Leah V. Goulding ◽

Joe James ◽

Juan Pu ◽

...

Keyword(s):

Influenza Virus ◽

Respiratory Syncytial Virus ◽

Influenza A Virus ◽

Broad Spectrum ◽

Influenza A ◽

Respiratory Viruses ◽

Influenza Viruses ◽

Virus Challenge ◽

2009 H1n1 ◽

Syncytial Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

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STUDIES ON INFLUENZA VIRUS

Journal of Experimental Medicine ◽

10.1084/jem.73.5.581 ◽

1941 ◽

Vol 73 (5) ◽

pp. 581-599 ◽

Cited By ~ 18

Author(s):

Edwin H. Lennette ◽

Frank L. Horsfall

Keyword(s):

Influenza Virus ◽

Chick Embryo ◽

Influenza A Virus ◽

Influenza A ◽

Complement Fixation ◽

Soluble Antigen ◽

Swine Virus ◽

Specific Fixation ◽

Mouse Lungs

Influenza complement fixation tests designed for use with ferret serum are described. Complement-fixing antigens derived from influenza ferret lungs were unsatisfactory due to their low content of soluble antigen; those prepared from mouse lungs or developing chick embryo membranes proved to be better antigenically and were reliable when the various reagents in the test were properly adjusted to eliminate non-specific fixation of complement. The results of cross complement fixation tests indicated that the soluble antigens of the PR8 and W.S. strains of influenza A virus were closely similar, if not identical. They indicated also that the soluble antigen of swine virus possessed components present in the antigens of the human strains of virus.

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