scholarly journals A Genetic Approach to Variation in Influenza Viruses: 3. Recombination of Characters in Influenza Virus Strains Used in Mixed Infections

1951 ◽  
Vol 5 (1) ◽  
pp. 59-66 ◽  
Author(s):  
F. M. BURNET ◽  
P. E. LIND
Keyword(s):  
Influenza Virus ◽  
Influenza Viruses ◽  
Mixed Infections ◽  
Genetic Approach ◽  
Virus Strains

Inhibition of ciliary activity in organ cultures of ferret trachea in reference to genetic and biological characters of influenza virus strains

1982 ◽  
Vol 28 (7) ◽  
pp. 809-814 ◽  
Author(s):  
P. Diaz-Rodriguez ◽  
A. Boudreault
Keyword(s):  
Influenza Virus ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Ciliary Activity ◽  
Organ Cultures ◽  
Preliminary Screening ◽  
Cold Adapted ◽  
Activity Inhibition ◽  
Biological Characters ◽  
Virus Strains

As reported previously, attenuated stable inhibitor-resistant influenza viruses can be screened by a 50% ciliary activity inhibition test in ferret tracheal organ cultures. This test was further applied to 5 attenuated cold-adapted influenza strains and to 11 strains with known a percentage of RNA–RNA hybridization with the parental A/PR/8/34 (H0N1) virus strain. Again, with one exception, attenuated strains could be clearly differentiated from virulent ones. It was concluded that virulence of influenza strains for man can be detected using this test regardless of the techniques used to prepare attenuated variants. A preliminary screening of attenuated candidates for live influenza vaccines can be achieved with confidence on ferret tracheal organ cultures.

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

2008 ◽  
Vol 82 (24) ◽  
pp. 12241-12251 ◽  
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.

scholarly journals The analysis of the monoclonal immune response to influenza virus. II. The antigenicity of the viral hemagglutinin.

1976 ◽  
Vol 144 (4) ◽  
pp. 985-995 ◽  
Author(s):  
W Gerhard
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Influenza Viruses ◽  
Antigenic Determinants ◽  
Humoral Immune ◽  
Viral Hemagglutinin ◽  
Or Groups ◽  
Virus Strains

The antigenicity of the hemagglutinins (HA) of five influenza viruses of the A0 and A1 subtypes has been analyzed by means of monoclonal antibodies of murine origin produced in vitro. Secondary monoclonal anti-HA(PR8) antibodies were able to differentiate 14 antigenic determinants (or groups of determinants) on the HA of five influenza virus strains of the A0 and A1 subtypes. Taking into account that certain pairs of determinants delineated on heterologous HA may reflect the heterogeneity of the humoral immune response to a single homologous determinant, the presence of at least eight determinants (host cell-derived determinants not included) on the homologous HA of PR8 and probably on the HA of influenza viruses in general is postulated. Three types of HA-determinants of A0 and A1 influenza virus strains could be distinguished: strain-specific, partially shared, and determinant(s) common to all five virus strains tested. Roughly 40, 55, and 5%, respectively, of the secondary anti-PR8 antibodies of BALB/c mice were directed against determinants belonging to either of the three types.

The cap-binding site of influenza virus protein PB2 as a drug target

2016 ◽  
Vol 72 (2) ◽  
pp. 245-253 ◽  
Author(s):  
Chelsea Severin ◽  
Tales Rocha de Moura ◽  
Yong Liu ◽  
Keqin Li ◽  
Xiaofeng Zheng ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Binding Site ◽  
Structural Changes ◽  
Hydrophobic Interactions ◽  
Influenza Viruses ◽  
Virus Protein ◽  
Mrna Transcription ◽  
Viral Mrnas ◽  
Multiple Strains ◽  
Virus Strains

The RNA polymerase of influenza virus consists of three subunits: PA, PB1 and PB2. It uses a unique `cap-snatching' mechanism for the transcription of viral mRNAs. The cap-binding domain of the PB2 subunit (PB2cap) in the viral polymerase binds the cap of a host pre-mRNA molecule, while the endonuclease of the PA subunit cleaves the RNA 10–13 nucleotides downstream from the cap. The capped RNA fragment is then used as the primer for viral mRNA transcription. The structure of PB2cap from influenza virus H1N1 A/California/07/2009 and of its complex with the cap analog m7GTP were solved at high resolution. Structural changes are observed in the cap-binding site of this new pandemic influenza virus strain, especially the hydrophobic interactions between the ligand and the target protein. m7GTP binds deeper in the pocket than some other virus strains, much deeper than the host cap-binding proteins. Analysis of the new H1N1 structures and comparisons with other structures provide new insights into the design of small-molecule inhibitors that will be effective against multiple strains of both type A and type B influenza viruses.

scholarly journals Development of a Pan-H1 Influenza Vaccine

2018 ◽  
Vol 92 (22) ◽  
Author(s):  
Nicole Darricarrère ◽  
Svetlana Pougatcheva ◽  
Xiaochu Duan ◽  
Rebecca S. Rudicell ◽  
Te-Hui Chou ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
The Past ◽  
Individual Strain ◽  
Humoral Responses ◽  
Virus Strains

ABSTRACT The efficacy of current seasonal influenza vaccines varies greatly, depending on the match to circulating viruses. Although most vaccines elicit strain-specific responses, some present cross-reactive epitopes that elicit antibodies against diverse viruses and remain unchanged and effective for several years. To determine whether combinations of specific H1 hemagglutinin (HA) antigens stimulate immune responses that protect against diverse H1 influenza viruses, we evaluated the antibody responses elicited by HA-ferritin nanoparticles derived from six evolutionarily divergent H1 sequences and two computationally optimized broadly reactive antigen (COBRA) HA antigens. Humoral responses were assessed against a panel of 16 representative influenza virus strains from the past 80 years. HAs from the strains A/NewCaledonia/20/1999 (NC99), A/California/04/2009 (CA09), A/HongKong/117/1977 (HK77), COBRA X6, or P1 elicited neutralization against diverse strains, and a combination of three wild-type HA or two COBRA HA nanoparticles conferred significant additional breadth beyond that observed with any individual strain. Therefore, combinations of H1 HAs may constitute a pan-H1 influenza vaccine. IMPORTANCE Seasonal influenza vaccines elicit strain-specific immune responses designed to protect against circulating viruses. Because these vaccines often show limited efficacy, the search for a broadly protective seasonal vaccine remains a priority. Among different influenza virus subtypes, H1N1 has long been circulating in humans and has caused pandemic outbreaks. In order to assess the potential of a multivalent HA combination vaccine to improve the breadth of protection against divergent H1N1 viruses, HA-ferritin nanoparticles were made and evaluated in mice against a panel of historical and contemporary influenza virus strains. Trivalent combinations of H1 nanoparticles improved the breadth of immunity against divergent H1 influenza viruses.

scholarly journals New aspects of influenza viruses.

1992 ◽  
Vol 5 (1) ◽  
pp. 74-92 ◽  
Author(s):  
M W Shaw ◽  
N H Arden ◽  
H F Maassab
Keyword(s):  
Influenza Virus ◽  
Antigenic Variation ◽  
Antiviral Agents ◽  
Molecular Techniques ◽  
Influenza Viruses ◽  
Virus Infections ◽  
Promising Alternative ◽  
Live Attenuated Influenza Virus ◽  
Virus Strains ◽  
Substantial Morbidity

Influenza virus infections continue to cause substantial morbidity and mortality with a worldwide social and economic impact. The past five years have seen dramatic advances in our understanding of viral replication, evolution, and antigenic variation. Genetic analyses have clarified relationships between human and animal influenza virus strains, demonstrating the potential for the appearance of new pandemic reassortants as hemagglutinin and neuraminidase genes are exchanged in an intermediate host. Clinical trials of candidate live attenuated influenza virus vaccines have shown the cold-adapted reassortants to be a promising alternative to the currently available inactivated virus preparations. Modern molecular techniques have allowed serious consideration of new approaches to the development of antiviral agents and vaccines as the functions of the viral genes and proteins are further elucidated. The development of techniques whereby the genes of influenza viruses can be specifically altered to investigate those functions will undoubtedly accelerate the pace at which our knowledge expands.

scholarly journals Targeting Antigens for Universal Influenza Vaccine Development

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 973
Author(s):  
Quyen-Thi Nguyen ◽  
Young-Ki Choi
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Influenza Viruses ◽  
Target Antigen ◽  
Cell Responses ◽  
Universal Influenza Vaccine ◽  
Virus Strains

Traditional influenza vaccines generate strain-specific antibodies which cannot provide protection against divergent influenza virus strains. Further, due to frequent antigenic shifts and drift of influenza viruses, annual reformulation and revaccination are required in order to match circulating strains. Thus, the development of a universal influenza vaccine (UIV) is critical for long-term protection against all seasonal influenza virus strains, as well as to provide protection against a potential pandemic virus. One of the most important strategies in the development of UIVs is the selection of optimal targeting antigens to generate broadly cross-reactive neutralizing antibodies or cross-reactive T cell responses against divergent influenza virus strains. However, each type of target antigen for UIVs has advantages and limitations for the generation of sufficient immune responses against divergent influenza viruses. Herein, we review current strategies and perspectives regarding the use of antigens, including hemagglutinin, neuraminidase, matrix proteins, and internal proteins, for universal influenza vaccine development.

scholarly journals Annexin II Incorporated into Influenza Virus Particles Supports Virus Replication by Converting Plasminogen into Plasmin

2008 ◽  
Vol 82 (14) ◽  
pp. 6820-6828 ◽  
Author(s):  
Fanny LeBouder ◽  
Eric Morello ◽  
Guus F. Rimmelzwaan ◽  
Françoise Bosse ◽  
Christine Péchoux ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Replication ◽  
Competitive Inhibitor ◽  
Cellular Protein ◽  
Influenza Viruses ◽  
Annexin Ii ◽  
Virus Particles ◽  
Influenza Virus Replication ◽  
Virus Strains ◽  
Host Cellular Protein

ABSTRACT For influenza viruses to become infectious, the proteolytic cleavage of hemagglutinin (HA) is essential. This usually is mediated by trypsin-like proteases in the respiratory tract. The binding of plasminogen to influenza virus A/WSN/33 leads to the cleavage of HA, a feature determining its pathogenicity and neurotropism in mice. Here, we demonstrate that plasminogen also promotes the replication of other influenza virus strains. The inhibition of the conversion of plasminogen into plasmin blocked influenza virus replication. Evidence is provided that the activation of plasminogen is mediated by the host cellular protein annexin II, which is incorporated into the virus particles. Indeed, the inhibition of plasminogen binding to annexin II by using a competitive inhibitor inhibits plasminogen activation into plasmin. Collectively, these results indicate that the annexin II-mediated activation of plasminogen supports the replication of influenza viruses, which may contribute to their pathogenicity.

scholarly journals ANTIVIRAL EFFECT OF «KAGOCEL» SUBSTANCE IN VITRO ON INFLUENZA VIRUSES H1N1, H1N1PDM09 AND H3N2

2019 ◽  
Vol 64 (3) ◽  
pp. 125-131 ◽  
Author(s):  
I. T. Fediakina ◽  
M. V. Konopleva ◽  
E. S. Proshina ◽  
E. V. Linnik ◽  
N. I. Nikitina
Keyword(s):  
Influenza Virus ◽  
Puerto Rico ◽  
Hong Kong ◽  
Mdck Cells ◽  
Influenza Viruses ◽  
Viral Antigens ◽  
Antiviral Efficacy ◽  
2009 H1n1 ◽  
Virus Strains

Introduction. Active circulation of pandemic influenza and new variants of influenza H3N2 strains requires monitoring of antiviral efficacy of drugs permitted for influenza therapy in the Russian Federation. Purpose. Assessment of antiviral efficacy of «Kagocel» substance against influenza viruses H1N1, H1N1pdm09 and H3N2 in vitro. Material and methods. Cytotoxic effect of «Kagocel» substance on MDCK cells had been determined by stained with MTS. Antiviral efficacy of «Kagocel» substance against influenza infection has been studied in vitro in the culture of MDCK cells infected with influenza virus strains: A/Puerto Rico/8/34 (H1N1), А/California/7/2009 (H1N1)pdm09, А/Hong Kong/1/68 (H3N2) and А/Hong Kong/4801/2014 (H3N2). The antiviral activity of «Kagocel» substance was tested by its effect on the infectious titer of the influenza viruses and on its impact on the expression level of viral antigens in the enzyme immunoassay test system. Results. «Kagocel» substance had low toxicity for MDCK cells. «Kagocel» inhibited the infection titer of influenza virus strains A/Puerto Rico/8/34 (H1N1), А/California/7/2009 (H1N1)pdm09, А/Hong Kong/1/68 (H3N2) and А/ Hong Kong /4801/2014 (H3N2) in the MDCK cell culture with equal efficacy. Study of the impact of «Kagocel» substance on the expression level of viral antigens by ELISA also revealed its antiviral efficacy for all tested strains. Dose dependence was observed from concentration of substance and from infective dose of virus. Discussion. Effective suppression of the reproduction of influenza virus strains A(H1N1), A(Н1N1)pdm09 and A(H3N2) in the different sublines of MDCK cells with «Kagocel» was shown by the different methods. These results give the possibility to suggest that along with the ability to induce interferons, «Kagocel» can impact on the reproduction of influenza virus, but the further research is needed. Conclusion. «Kagocel» substance effectively inhibits the reproduction of influenza virus strains A(H1N1), A(Н1N1)pdm09 and A(H3N2) in vitro. At the same time, the selectivity index is quite high.

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