scholarly journals A haemagglutinin (HA1)-specific FAb neutralizes influenza A virus by inhibiting fusion activity

2001 ◽  
Vol 82 (6) ◽  
pp. 1387-1395 ◽  
Author(s):  
M. J. Edwards ◽  
N. J. Dimmock
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Antigenic Site ◽  
Detectable Effect ◽  
Target Cells ◽  
Fusion Activity ◽  
Influenza Virus A ◽  
Virus Attachment ◽  
Virus Fusion

H9-D3-4R2 (referred to as H9), a murine monoclonal HA1-specific IgG3, recognizes an epitope within antigenic site Cb of influenza virus A/PR/8/34 (H1N1). At 50% neutralization, inhibition of virus-mediated fusion was responsible for the majority of neutralization but, at higher antibody concentrations, the attachment of virus to target cells was also inhibited and may have contributed to neutralization. H9 FAb was also neutralizing, although the concentration needed was two orders of magnitude greater than for the IgG. Functional affinity of the IgG and affinity of the FAb were almost identical, and it is not clear why the neutralization efficiency of the FAb was so low. Unlike its IgG, H9 FAb had no detectable effect on virus attachment but inhibited virus fusion activity. It thus appears that monovalent binding by this antibody is sufficient to inhibit fusion activity and that this was directly responsible for neutralization of infectivity.

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

Viruses ◽  
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.

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

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.

scholarly journals Development of DNA-Biochip for Identification of Influenza A Virus Subtypes

2012 ◽  
pp. 89-93
Author(s):  
A. N. Shikov ◽  
E. I. Sergeeva ◽  
O. K. Demina ◽  
V. A. Ternovoy ◽  
V. V. Ryabinin ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Highly Pathogenic Avian Influenza ◽  
Influenza Viruses ◽  
Highly Pathogenic ◽  
Influenza Virus A ◽  
Pathogenic Avian Influenza ◽  
Pathogenic Avian Influenza Virus

Developed was the DNA-biochip to identify subtypes of influenza A virus, pathogenic for humans. Microchip was capable of detecting H1, H3, H5-subtypes of hemagglutinin (including H1-subtype of pandemic A/H1N1(2009) influenza virus ) and neuraminidase subtypes N1,N2 of influenza virus. This microchip was successfully tested on the strains of A/H5N1 highly pathogenic avian influenza virus, A/H1N1(2009) pandemic influenza virus, A/H1N1 and A/H3N2 seasonal influenza viruses.

scholarly journals A reverse-genetics system for Influenza A virus using T7 RNA polymerase

2007 ◽  
Vol 88 (4) ◽  
pp. 1281-1287 ◽  
Author(s):  
Emmie de Wit ◽  
Monique I. J. Spronken ◽  
Gaby Vervaet ◽  
Guus F. Rimmelzwaan ◽  
Albert D. M. E. Osterhaus ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Rna Polymerase ◽  
Influenza A Virus ◽  
Influenza A ◽  
Reverse Genetics ◽  
T7 Rna Polymerase ◽  
Influenza Virus A ◽  
Sense Orientation ◽  
Polymerase I ◽  
Rna Polymerase Promoter

The currently available reverse-genetics systems for Influenza A virus are all based on transcription of genomic RNA by RNA polymerase I, but the species specificity of this polymerase is a disadvantage. A reverse-genetics vector containing a T7 RNA polymerase promoter, hepatitis delta virus ribozyme sequence and T7 RNA polymerase terminator sequence has been developed. To achieve optimal expression in minigenome assays, it was determined that viral RNA should be inserted in this vector in the negative-sense orientation with two additional G residues downstream of the T7 RNA polymerase promoter. It was also shown that expression of the minigenome was more efficient when a T7 RNA polymerase with a nuclear-localization signal was used. By using this reverse-genetics system, recombinant influenza virus A/PR/8/34 was produced more efficiently than by using a similar polymerase I-based reverse-genetics system. Furthermore, influenza virus A/NL/219/03 could be rescued from 293T, MDCK and QT6 cells. Thus, a reverse-genetics system for the rescue of Influenza A virus has been developed, which will be useful for fundamental research and vaccine seed strain production in a variety of cell lines.

scholarly journals Heterosubtypic Antibodies to Influenza A Virus Have Limited Activity against Cell-Bound Virus but Are Not Impaired by Strain-Specific Serum Antibodies

2014 ◽  
Vol 89 (6) ◽  
pp. 3136-3144 ◽  
Author(s):  
Arkadiusz Wyrzucki ◽  
Matteo Bianchi ◽  
Ines Kohler ◽  
Marco Steck ◽  
Lars Hangartner
Keyword(s):  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Influenza A Virus ◽  
Influenza A ◽  
Natural Infection ◽  
Influenza Virus Vaccine ◽  
Serum Antibodies ◽  
Virus Attachment ◽  
Endosomal Membrane ◽  
Multiple Strains

ABSTRACTThe majority of influenza virus-specific antibodies elicited by vaccination or natural infection are effective only against the eliciting or closely related viruses. Rare stem-specific heterosubtypic monoclonal antibodies (hMAbs) can neutralize multiple strains and subtypes by preventing hemagglutinin (HA)-mediated fusion of the viral membrane with the endosomal membrane. The epitopes recognized by these hMAbs are therefore considered promising targets for the development of pan-influenza virus vaccines. Here, we report the isolation of a novel human HA stem-reactive monoclonal antibody, hMAb 1.12, with exceptionally broad neutralizing activity encompassing viruses from 15 distinct HA subtypes. Using MAb 1.12 and two other monoclonal antibodies, we demonstrate that neutralization by hMAbs is virtually irreversible but becomes severely impaired following virus attachment to cells. In contrast, no interference by human anti-influenza virus serum antibodies was found, indicating that apically binding antibodies do not impair access to the membrane-proximal heterosubtypic epitopes. Our findings therefore encourage development of new vaccine concepts aiming at the induction of stem-specific heterosubtypic antibodies, as we provide support for their effectiveness in individuals previously exposed to influenza virus.IMPORTANCEThe influenza A virus hemagglutinin (HA) can easily accommodate changes in its antigenic structures to escape preexisting immunity. This variability restricts the breadth and long-term efficacy of influenza vaccines. Only a few heterosubtypic antibodies (hMAbs), i.e., antibodies that can neutralize more than one subtype of influenza A virus, have been identified. The molecular interactions between these heterosubtypic antibodies and hemagglutinin are well characterized, yet little is known about the functional properties of these antibodies. Using a new, extraordinarily broad hMAb, we show that virus neutralization by hMAbs is virtually irreversible and that efficient neutralization is possible only if stem-specific hMAbs bind to HA before the virus attaches to the cell surface. No interference between strain-specific human serum immunoglobulin and hMAbs was found, indicating that preexisting humoral immunity to influenza virus does not limit the efficacy of stem-reactive heterosubtypic antibodies. This knowledge supports the development of a pan-influenza virus vaccine.

scholarly journals Identification of viral molecules recognized by influenza-specific human cytotoxic T lymphocytes.

1987 ◽  
Vol 165 (2) ◽  
pp. 408-416 ◽  
Author(s):  
F Gotch ◽  
A McMichael ◽  
G Smith ◽  
B Moss
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Cytotoxic T Cells ◽  
Viral Proteins ◽  
Target Cells ◽  
Gene Products ◽  
Virus Surface ◽  
Vaccinia Viruses ◽  
The Matrix

Human cytotoxic T cells specific for influenza A virus were tested for recognition of each of the ten influenza A virus proteins expressed in target cells using recombinant vaccinia viruses. They recognized the matrix M1, polymerase PB2, and nucleoproteins of influenza virus in association with MHC class I antigens. These internal viral proteins were seen by CTL in conjunction with one or more of the available dependent HLA gene products. There was no detectable recognition of influenza virus surface glycoproteins in target cells.

scholarly journals A Mutation in the HLA-B*2705-Restricted NP383-391 Epitope Affects the Human Influenza A Virus-Specific Cytotoxic T-Lymphocyte Response In Vitro

2004 ◽  
Vol 78 (10) ◽  
pp. 5216-5222 ◽  
Author(s):  
E. G. M. Berkhoff ◽  
A. C. M. Boon ◽  
N. J. Nieuwkoop ◽  
R. A. M. Fouchier ◽  
K. Sintnicolaas ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza A Viruses ◽  
Ctl Response ◽  
Influenza Virus A ◽  
Ctl Epitope ◽  
Ifn Γ

ABSTRACT Viruses can exploit a variety of strategies to evade immune surveillance by cytotoxic T lymphocytes (CTL), including the acquisition of mutations in or adjacent to CTL epitopes. Recently, an amino acid substitution (R384G) in an HLA-B*2705-restricted CTL epitope in the influenza A virus nucleoprotein (nucleoprotein containing residues 383 to 391 [NP383-391]; SRYWAIRTR, where R is the residue that was mutated) was associated with escape from CTL-mediated immunity. The effect of this mutation on the in vitro influenza A virus-specific CTL response was studied. To this end, two influenza A viruses, one with and one without the NP383-391 epitope, were constructed by reverse genetics and designated influenza viruses A/NL/94-384R and A/NL/94-384G, respectively. The absence of the HLA-B*2705-restricted CTL epitope in influenza virus A/NL/94-384G was confirmed by using 51Cr release assays with a T-cell clone specific for the NP383-391 epitope. In addition, peripheral blood mononuclear cells (PBMC) stimulated with influenza virus A/NL/94-384G failed to recognize HLA-B*2705-positive target cells pulsed with the original NP383-391 peptide. The proportion of virus-specific CD8+ gamma interferon (IFN-γ)-positive T cells in in vitro-stimulated PBMC was determined by intracellular IFN-γ staining after restimulation with virus-infected autologous B-lymphoblastoid cell lines and C1R cell lines expressing only HLA-B*2705. The proportion of virus-specific CD8+ T cells was lower in PBMC stimulated in vitro with influenza virus A/NL/94-384G obtained from several HLA-B*2705-positive donors than in PBMC stimulated with influenza virus A/NL/94-384R. This finding indicated that amino acid variations in CTL epitopes can affect the virus-specific CTL response and that the NP383-391 epitope is the most important HLA-B*2705-restricted epitope in the nucleoprotein of influenza A viruses.

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