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      Influenza

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          Abstract

          Influenza is an infectious respiratory disease that, in humans, is caused by influenza A and influenza B viruses. Typically characterized by annual seasonal epidemics, sporadic pandemic outbreaks involve influenza A virus strains of zoonotic origin. The WHO estimates that annual epidemics of influenza result in ~1 billion infections, 3–5 million cases of severe illness and 300,000–500,000 deaths. The severity of pandemic influenza depends on multiple factors, including the virulence of the pandemic virus strain and the level of pre-existing immunity. The most severe influenza pandemic, in 1918, resulted in >40 million deaths worldwide. Influenza vaccines are formulated every year to match the circulating strains, as they evolve antigenically owing to antigenic drift. Nevertheless, vaccine efficacy is not optimal and is dramatically low in the case of an antigenic mismatch between the vaccine and the circulating virus strain. Antiviral agents that target the influenza virus enzyme neuraminidase have been developed for prophylaxis and therapy. However, the use of these antivirals is still limited. Emerging approaches to combat influenza include the development of universal influenza virus vaccines that provide protection against antigenically distant influenza viruses, but these vaccines need to be tested in clinical trials to ascertain their effectiveness.

          Abstract

          Influenza is an infectious respiratory disease that, in humans, is caused by influenza A and influenza B viruses. This Primer discusses the biological features of influenza viruses, their effects on human and animal health and the mitigation strategies to reduce the burden of this disease.

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          Most cited references169

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          RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates.

          Double-stranded RNA (dsRNA) produced during viral replication is believed to be the critical trigger for activation of antiviral immunity mediated by the RNA helicase enzymes retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). We showed that influenza A virus infection does not generate dsRNA and that RIG-I is activated by viral genomic single-stranded RNA (ssRNA) bearing 5'-phosphates. This is blocked by the influenza protein nonstructured protein 1 (NS1), which is found in a complex with RIG-I in infected cells. These results identify RIG-I as a ssRNA sensor and potential target of viral immune evasion and suggest that its ability to sense 5'-phosphorylated RNA evolved in the innate immune system as a means of discriminating between self and nonself.
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            Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses.

            M Hatta (2001)
            In 1997, an H5N1 influenza A virus was transmitted from birds to humans in Hong Kong, killing 6 of the 18 people infected. When mice were infected with the human isolates, two virulence groups became apparent. Using reverse genetics, we showed that a mutation at position 627 in the PB2 protein influenced the outcome of infection in mice. Moreover, high cleavability of the hemagglutinin glycoprotein was an essential requirement for lethal infection.
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              Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls.

              In wild aquatic birds and poultry around the world, influenza A viruses carrying 15 antigenic subtypes of hemagglutinin (HA) and 9 antigenic subtypes of neuraminidase (NA) have been described. Here we describe a previously unidentified antigenic subtype of HA (H16), detected in viruses circulating in black-headed gulls in Sweden. In agreement with established criteria for the definition of antigenic subtypes, hemagglutination inhibition assays and immunodiffusion assays failed to detect specific reactivity between H16 and the previously described subtypes H1 to H15. Genetically, H16 HA was found to be distantly related to H13 HA, a subtype also detected exclusively in shorebirds, and the amino acid composition of the putative receptor-binding site of H13 and H16 HAs was found to be distinct from that in HA subtypes circulating in ducks and geese. The H16 viruses contained NA genes that were similar to those of other Eurasian shorebirds but genetically distinct from N3 genes detected in other birds and geographical locations. The European gull viruses were further distinguishable from other influenza A viruses based on their PB2, NP, and NS genes. Gaining information on the full spectrum of avian influenza A viruses and creating reagents for their detection and identification will remain an important task for influenza surveillance, outbreak control, and animal and public health. We propose that sequence analyses of HA and NA genes of influenza A viruses be used for the rapid identification of existing and novel HA and NA subtypes.
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                Author and article information

                Contributors
                adolfo.garcia-sastre@mssm.edu
                Journal
                Nat Rev Dis Primers
                Nat Rev Dis Primers
                Nature Reviews. Disease Primers
                Nature Publishing Group UK (London )
                2056-676X
                28 June 2018
                2018
                : 4
                : 1
                : 3
                Affiliations
                [1 ]ISNI 0000 0001 0670 2351, GRID grid.59734.3c, Department of Microbiology, , Icahn School of Medicine at Mount Sinai, ; New York, NY USA
                [2 ]ISNI 0000 0001 2180 6431, GRID grid.4280.e, Duke–NUS Medical School, ; Singapore, Singapore
                [3 ]ISNI 0000 0004 1936 7961, GRID grid.26009.3d, Duke Global Health Institute, , Duke University, ; Durham, NC USA
                [4 ]ISNI 000000040459992X, GRID grid.5645.2, Department of Viroscience, , Erasmus MC, ; Rotterdam, Netherlands
                [5 ]ISNI 0000000121742757, GRID grid.194645.b, WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, , The University of Hong Kong, Hong Kong Special Administrative Region, ; Hong Kong, China
                [6 ]ISNI 0000000121742757, GRID grid.194645.b, Center of Influenza Research, Li Ka Shing Faculty of Medicine, , The University of Hong Kong, Hong Kong Special Administrative Region, ; Hong Kong, China
                [7 ]ISNI 0000 0001 2179 088X, GRID grid.1008.9, Department of Microbiology and Immunology, , University of Melbourne at the Peter Doherty Institute for Infection and Immunity, ; Melbourne, Victoria Australia
                [8 ]ISNI 0000 0001 0224 711X, GRID grid.240871.8, Department of Immunology, , St Jude Children’s Research Hospital, ; Memphis, TN USA
                [9 ]ISNI 0000 0001 0670 2351, GRID grid.59734.3c, Division of Infectious Diseases, Department of Medicine, , Icahn School of Medicine at Mount Sinai, ; New York, NY USA
                [10 ]ISNI 0000 0004 1936 9166, GRID grid.412750.5, Division of Infectious Diseases, Department of Medicine, , University of Rochester School of Medicine and Dentistry, ; Rochester, NY USA
                [11 ]ISNI 0000 0001 0224 711X, GRID grid.240871.8, Department of Infectious Diseases, , St Jude Children’s Research Hospital, ; Memphis, TN USA
                [12 ]ISNI 0000 0001 0670 2351, GRID grid.59734.3c, Global Health and Emerging Pathogens Institute, , Icahn School of Medicine at Mount Sinai, ; New York, NY USA
                Article
                2
                10.1038/s41572-018-0002-y
                7097467
                29955068
                6f9e1dd3-96a8-4e9e-95de-78e20a4d0407
                © Macmillan Publishers Ltd., part of Springer Nature 2018

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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                Primer
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                © Macmillan Publishers Ltd., part of Springer Nature 2018

                influenza virus,vaccines,respiratory tract diseases,viral pathogenesis

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