Influenza(Virology)
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Influenza(Virology)

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    Influenza(Virology) Influenza(Virology) Presentation Transcript

    • Prepared by- Md.Riaz
    • Acquaintance  Influenza virus is a negative-sense single- stranded RNA virus under the orthomyxoviridae family. It causes Influenza disease commonly known as ‘Flu’.  Influenza is a highly contagious viral infection of the respiratory passages of birds and mammals including us can occur in epidemics.  It is the most familiar virus in this present world.
    • Orthomyxoviridae  Order : Mononegavirales  medium sized(80-120 nm), pleomorphic, enveloped  Genome: linear, segmented (6-8), (-)sense, single- stranded RNA, 10-13.6 kb  It has six genera, including genera:-  Influenzavirus A  Influenzavirus B  Influenzavirus C  cause respiratory illness with systemic symptoms.
    • History The word ‘Influenza’ comes from Italian language means ‘to influence’ that was first used by J. Hugger in 1703.  Hippocrates first made accurate description on it. In 1933 it discovered by the scientists: Christopher Andrews, Wilson Smith, and Patrick Laidlaw.
    • Electron-Micrograph
    • Morphology Influenza type A,B, and C are similar in structure. Those are roughly spherical of 80-120 nm in diameter but type-C may occur as filamentous.
    • Continued….  The outer layer is the lipid membrane, spikes are composed of glycoproteins: Hemagglutanin (HA) and Neuraminidase (NA). There present M2 protein embedded in lipid membrane and M1 protein beneath the lipid membrane.  The complete genome of Influenza is segmented into 8 fragments but 7 fragments in case of Influenza C. There total 11 genes are located in the genome encoded 11 proteins.  The genomic size is about 13.5 bp. * HA and NA proteins determine the subtype of influenza virus.
    • Continued…. NA= Neuraminidase HA= Hemagglutinin NP= Neucleoprotein NS1= Non-structural protein NS2(NEP)=mediates the export of RNP-complexes from nucleus. PB1, PB1-F2, PB2, PA = subunits of viral RNA polymerase and are all crucial for viral transcription and replication. M1= Matrix proteins form capside. M2= Proton-selective Ion-channel
    • Genome-organization
    • Variation  There are total 25 serotypes of Influenza: 16 HA and 9 NA varieties. Influenza A: most virulent human pathogen among influenza viruses, wide host-range, highest serotypes; cause severe disease including: Bird-flu(H5N1), Swine- flu(H1N1), become pandemics! Influenza B : mostly found in human and only two serotypes present. Influenza B don’t cause pandemics due to limited host range. Influenza C : It is milder and causes less severe disease. Don’t become endemic and no subtype present.
    • Hemagglutinin -Influenza virus surface glycoprotein, cylinder- shaped, consists of 549 amino acids. -It has a central alpha-helix coil and three spherical heads contain sialic acid binding sites -works in viral attachment with sialic acid receptor and in fusion of viral envelope with endosome. -There are at least 18 different HA antigens. H18 discovered in 2013.
    • Neuraminidase -Influenza virus surface glycoprotein - It has 9 different NA antigens - enzymatically cleaves the sialic acid groups from host cells, thus promote entry and replication. - promotes the release of progeny viruses - Target of antiviral drugs: Zanamvir, Oseltamivir
    • L i fe - c y c l e (Pathology)
    • Pathophysiology Influenza virus can infect both upper and lower respiratory tracts. Sialic acid on epithelial cells are the receptors.  The typical incubation period of influenza is 24 hours to 4 days with average: 2 days.  Children's are more readily affected than adults.
    • Symptoms  Fiver: 100°F to 104°F, can be raised to 106°F  Headache Dry cough runny nose, sore throat Fatigue (tiredness) Body aches and Myalgia
    • Transmission Influenza can be spread in three main ways: Direct transmission: an infected person frequently touch their nose, mouth or conjunctiva. Virus-laden aerosols: coughing, sneezing, speaking,normal breathing all produce aerosols. A good sneeze can generate up to 20,000 aerosols. Even a single droplet may cause infection. Droplet-nuclei (1-4 µm) suspended in the air for long period and spreads the disease much. Indirect transmission: through contaminated objects :called fomites, such as toys, doorknobs, light switches etc.
    • Diagnosis  Isolation -- Nose, throat swab -- Tissue culture  Serology  Rapid Test: ‘Rapid Influenza diagnostic test’ is most common done by swabbing nose and throat secretion. * Albeit, different tests and experiments the symptoms associated with Influenza are most important tools to become identified as an Influenza patient. Call your doctor when: Difficulty breathing or shortness of breath  Pain or pressure in the chest or abdomen  Dizziness  Confusion  Severe or persistent vomiting
    • Treatments It includes a range of medications and therapies:- Antiviral drugs: a. Oseltamivir: serving as competitive inhibitor of the activity of viral neuraminidase enzyme on sialic acid. b. Zanamivir: works by binding to the active site of the neuraminidase protein, rendering the influenza virus unable to escape its host cell. c. M2 inhibitors: The antiviral drugs such as- Amantadine and Rimantadine block a viral ion channel (M2 protein) and prevent the virus from infecting cells.
    • Symptomatic treatments CDC recommends persons suffering from Influenza:  Stay at home  Get plenty of rest  Drink lots of liquids  Don’t smoke and avoid alcohol  Remain alert for emergency warning signs
    • Vaccination  Annual vaccination for a given year. Each seasonal vaccine contains three/four viral-strain antigens: Type A H1N1 Type B H3N2 Type B strains * CDC said that Flu vaccine is 61% effective and recommends flu vaccination for all over 6 months. Side effect: There is no severe side-effects of influenza vaccine. Sometimes allergic reaction and increased cough, runny nose, asthma are identified in childrens.
    • Continued… • Inactivated subunit (TIV/QIV) – intramuscular – trivalent or quardivalent – split virus and subunit types (killed) – duration of immunity 1 year or less • Live attenuated vaccine (LAIV) – intranasal – Trivalent – live attenuated – duration of immunity at least 1 year
    • Interferon The Alpha/Beta Interferon Receptor Provides Protection against Influenza Virus Replication IFN-gamma treatment at early stages of influenza virus infection protects mice from death in a NK cell-dependent manner.  Side-effects: Fever Malaise Muscle pain Fatigue
    • Prevention • Get vaccinated each year •Washing hands • Covering nose and mouth while coughing, sneezing • Avoid touching nose, mouth, eyes • Limited contact with sick people.
    • Antigenic Drift Due to the absence of proofreading activity, the RNA- dependent RNA polymerase copies the viral genome making error roughly in every 10 thousand nucleotides (which is the approximate length of the influenza vRNA). Hence, the majority of newly assembled influenza viruses are mutants, thus the antibody-binding sites become changed. This is called antigenic-drift.  caused by point mutation  change in HA and NA  results in epidemics  eg. outbreak of influenza A H3N2 (2003-2004)  occurs in all type A, B and C
    • Continued…
    • Antigenic Shift When more than one type of influenza virus infects a single cell the separation of viral genome into eight separated segments allows mixing or reassortment of new viral RNAs that induces new strains of influenza virus. This process called antigenic-shift. It occurs only in influenza Type A.  caused by exchange of genetic materials (RNA)  new strains generate  results in pandemics  eg. Asian flu by H2N2 subtype in 1958-1959.  only in influenza type A
    • Continued…
    • Pandemic (Influenza) Name of Pandemic Date Deaths Spanish flu 1918-1920 20-100 million Asian flu 1957-1958 1-1.5 million Hong Kong flu 1968-1969 .75-1.0 million Russian flu 1977-1978 No accurate count. 2009 flu pandemic 2009-2010 18,000
    • Influenza A (H1N1) pandemic: 2009 .
    • Pandemic:2009 The H1N1 resulted when a previous triple reassortment of bird, swine and human flu viruses further combined with a Eurasian pig flu virus and spreads out Swine flu.  The outbreak was first detected in Mexico City on 18 March 2009  Total 14,286 people have been died worldwide. U.S. president Barack Obama being vaccinated against H1N1 flu on 20 December 2009
    • Current-Research • Influenza Genome Sequencing Project (IGSP): creating a library of influenza sequences to clarify which factors make one strain more lethal than another. As of mid-2008, over 3000 isolates had been completely sequenced. • Research into new vaccines : the generation of new vaccine strains . The most remarkable is: research on a universal influenza A vaccine, targeted against the M2 protein is being done at the University of Ghent by Walter Fiers,Xavier Saelens and their team and now under clinical trials. • Study the infection in other animals especially birds.
    • Avian flu *Avian influenza known as bird-flu. All known viruses that cause influenza in birds belong to the species influenza A virus. *Most highly pathogenic strain H5N1 had been spreading throughout Asia since 2003 and reached to Europe In 2005. *There are many subtypes of AIV: H5N1, H7N3, H7N7 H7N9, and H9N2
    • Swine flu *Swine flu also known as ‘Pig influenza’. It is caused by Swine influenza viruses including Influenza C and Influenza A subtypes: H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3. * Direct transmission of an influenza virus from pigs to humans is occasionally possible. * In 2009, a swine-origin H1N1 virus strain commonly referred to as "swine flu" caused the ‘2009 flu pandemic’.
    • Flu in Bangladesh Institute of Epidemiology, Disease Control and Research (IEDCR), ICDDRB, CDC (Bangladesh branch) are disease monitoring arm. Bangladesh notified its first infection on May 22, 2008 Four flu viruses –H1N1, H5N1, H3N2 and H9N2— are circulating in Bangladesh.