Influenza virus

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Daniel S. Marín VIRUS DE LA INFLUENZA

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Daniel S. MarnVIRUS DE LA INFLUENZA

N Engl J Med 2015;373:415-27

N Engl J Med 2015;373:415-27

J. E. Bennett, R. Dolin, M. J. Blaser, Mandell, Douglas, and Bennett's principles and practice of infectious diseases. (Elsevier Health Sciences, 2014).

A y B causan brotes epidmicosC enfermedad respiratoria espordicaH1-H16N1-N9Influenza B victoria y yamagata lineage

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J. E. Bennett, R. Dolin, M. J. Blaser, Mandell, Douglas, and Bennett's principles and practice of infectious diseases. (Elsevier Health Sciences, 2014).

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J. E. Bennett, R. Dolin, M. J. Blaser, Mandell, Douglas, and Bennett's principles and practice of infectious diseases. (Elsevier Health Sciences, 2014).

HA 1.- Participar en la adsorcin y penetracin del virus a la clula2.- Estimular la fusin entre la membrana de la clula husped y la envoltura viral 3.- Aglutinar a los eritrocitos a travs de la HA1, produciendo una reaccin de hemaglutinacin visible 4.- Inducir la sntesis de anticuerpos Neutralizantes

NA1.- Catalizar clivaje de las uniones entre el cido silico terminal y un residuo azucarado adyacente celular que permite transportar al virus a travs de las mucinas y destruir los receptores de la HA sobre la clula husped, permitiendo la elucin de la progenie viral de la clula infectada2.- Prevenir la agregacin viral, protegiendo al virus de su propia HA 3.- Estimular la produccin de anticuerpos inhibidores de la neuraminidasa 7

Nature Reviews Microbiology6,143-155

On different cell types from those affected by HIV-1, influenza virus binds via haemagglutinin 1 (HA1) to terminal sialic acids present on glycoproteins or on glycolipids (step1b). The virus is subsequently internalized by receptor-mediated endocytosis into a low pH compartment (endosome), triggering conformational changes that expose the viral fusion peptide that is located in HA2 (step2b). Subsequently, the genomic ribonucleoprotein complex is transported to the nucleus to initiate transcription and replication of the viral genome (step3b).8

J. E. Bennett, R. Dolin, M. J. Blaser, Mandell, Douglas, and Bennett's principles and practice of infectious diseases. (Elsevier Health Sciences, 2014).

the level of excess mortality is highest in years when influenza A/ H3N2 viruses predominate, but influenza B and, to a lesser extent, A/H1N1 viruses also can be associated with excess mortality. Because 9

J. E. Bennett, R. Dolin, M. J. Blaser, Mandell, Douglas, and Bennett's principles and practice of infectious diseases. (Elsevier Health Sciences, 2014).

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J. E. Bennett, R. Dolin, M. J. Blaser, Mandell, Douglas, and Bennett's principles and practice of infectious diseases.

H5N1 mortalidad 60% aproximadamenteMost cases have had close contact with ill poultry in the week before the onset of illness. Activities such as plucking and preparing diseased birds, playing with birds, especially asymptomatically infected ducks, and handling fighting cocks are risk factors for infection.H7N7 11

N Engl J Med 2005; 353:2209-2211

In 1918, an H1N1 virus closely related to avian viruses adapted to replicate efficiently in humans. In 1957 and in 1968, reassortment events led tonew viruses that resulted in pandemic influenza. The 1957 influenza virus (Asian influenza, an H2N2 virus) acquired three genetic segments from anavian species (a hemagglutinin, a neuraminidase, and a polymerase gene, PB1), and the 1968 influenza virus (Hong Kong influenza, an H3N2 virus)acquired two genetic segments from an avian species (hemagglutinin and PB1). Future pandemic strains could arise through either mechanism12

Fisiopatologa

J. E. Bennett, R. Dolin, M. J. Blaser, Mandell, Douglas, and Bennett's principles and practice of infectious diseases. (Elsevier Health Sciences, 2014).

Nature Reviews Microbiology12,252262(2014)

The interplay between virus, host and bacteria in co-infections. a | Several virulence factors that areexpressed by influenza viruses can directly interact with the lungs or with the host immune system. Haemagglutinin Nature Reviews | Microbiologymediates attachment by binding to terminal sialic acids on cell surface proteins and initiating endocytosis. A variety of extracellular proteins can bind to glycans on haemagglutinin and neutralize or help to eliminate viruses from the lowerrespiratory tract. Viruses with a poorly glycosylated haemagglutinin and the ability to engage both a2,3- and a2,6-linkedsialic acids as receptors are able to penetrate deep into the lungs. The sialidase activity of the neuraminidase proteincleaves sialic acids from the surface of epithelial cells and from mucins that try to bind and eliminate virions thisfacilitates bacterial access to receptors. The non-structural proteins PB1-F2 and NS1 are made in infected cells. PB1-F2causes cytotoxicity and promotes inflammatory responses to co-pathogens; NS1 modulates innate pathways, includinginterferon signalling. b | These virus-mediated effects engender changes in the physical properties of the lungs andcompromise innate immunity at several levels. Epithelial damage and increased receptor availability enable bacteria toadhere and grow. Depletion of the specific subset of lung macrophages that is functionally capable of phagocytosingbacteria enables escape from early innate immunity. Anergy of the primary bacterial sensing apparatus of the immunesystem, pattern recognition receptors, such as the Toll-like receptors (TLRs), prolongs this window of susceptibility forweeks, while a dysfunctional and paradoxically over-exuberant inflammatory response that is characterized by neutrophilinflux and cytokine storm furthers the acute lung injury that has been started by the virus. c | Bacteria that express specificvirulence factors may take advantage of these changes to the host, grow unchecked and cause disease. Adherencefactors, such as pneumococcal surface protein A or staphylococcal MSCRAMMs (microbial surface componentsrecognizing adhesive matrix molecules), enable bacteria to attach to newly uncovered receptors or to the matrix ofcollagen and fibrin that has been laid down as a scaffold for repair. Bacterial cytotoxins synergize with their viralcounterparts to further the physical and immune-mediated damage to the lungs. Specific characteristics of somebacterial strains, such as a thick, complement-resistant capsule, and a set of unknown proteins whose existence can beinferred but have not yet been described, enable improved survival, growth and pathology in virus-infected hosts.15

Nature Reviews Microbiology12,252262(2014)

Temporal associations between viral titre, bacterial load and theavailability of immune effectors in a model of viralbacterial co-infection. Influenzaviruses replicate rapidly when a primary infection is established, reaching a peak titre(blue line) in the lungs 23days after inoculation. Impairment of host defences, includinga swift depletion of alveolar macrophages (green line) over the first 3days of infectionenables superinfecting bacteria to grow rapidly (red line) and cause pneumonia. Therapid growth of bacteria is associated with a rebound in viral titre via unclear mechanisms.Failure of secondary immunity to control the co-infection can lead to uncheckedbacterial growth after viral clearance, resulting in morbidity and mortalit16

Presentacin clnicaInfluenza no complicada.

J. E. Bennett, R. Dolin, M. J. Blaser, Mandell, Douglas, and Bennett's principles and practice of infectious diseases. (Elsevier Health Sciences, 2014).

DIAGNOSTICOClnicoPruebas rpidasPruebas molecularesSerolgicosAislamiento del virus

TratamientoSeasonalOutbreakFamily

N Engl J Med 2005;353:1363-73.

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