Curs 1. Gripa 2014_2015

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Curs 1. Gripa 2014_2015

Text of Curs 1. Gripa 2014_2015

  • Infecia cu virusul gripal(Influenza)

    Influenza is one of the most important respiratory infections in humans. The term "influenza" actually dates back to the Middle Ages and is derived from the Latin word for occult or astral influence, as it seemingly appeared out of nowhere each winter and then vanished in the spring.

  • Clasificare(1). Treanor JJ. Orthomyxoviridae: Influenza virus In: Mandell. GL, Bennette JE., Dolin R, editors, Principles and Practice of Infectious Diseases. London: Churchill Livingstone, 6th Edition:2006(2). Fukuda K, Levandowski RA, Bridges C, Cox N. Inativated Influenza Vaccines. In Plotkin SA OW, editor. VACCINES, Philadelphia: Saunders, 2004: 339-388OrthomyxoviridaeTip ATip BTip CFamilia:



    Subtipuri(doar tipul A):

    Rezervor:Om, porc,cal, psri,mamifere marineOmOm, porcVirus ARNInfluenza C virusInfluenza virusH3N2Type A H1N1

    *Tipul ACel mai raspandit la om si animaleMare variabilitate geneticaFrecvent mutatii minore (epidemii) Rar mutatii majore (pandemii)Afecteaza toate varstele (gravitate mai mare la varstnici si tarati)

    Tipul BVariabilitate redusaRareori responsabil de epidemiiProduce indeosebi cazuri sporadice intre epidemiiForme clinice usoare (sunt afectati mai ales copiii)

    Tipul CNu produce epidemiiCazuri izolateForme clinice usoare sau asimptomaticeDupa 15 ani majoritatea populatiei are anticorpi specifici

    Influenza virus types A and B are both common causes of acute respiratory illnesses. Although both virus types may cause epidemics of considerable morbidity and mortality, influenza B infections are often limited to localized outbreaks; whereas influenza A viruses are the principal cause of larger epidemics including worldwide pandemics. (3)However, all three viruses share certain features that are fundamental to their biologic behavior, including the presence of a host-cell derived envelope, envelope glycoproteins of critical importance in virus entry and egress from cells, and a segmented genome of negative sense (i.e., opposite of message sense), single-stranded RNA.(4)

    (3). WHO Influenza Vaccine - accessed on May 20th 2006(4). Mandell. GL, Bennette JE., Dolin R, editors, Principles and Practice of Infectious Diseases. London: Churchill Livingstone, 6th Ed; 2006

  • Structura virusului gripal(1). Fukuda K, Levandowski RA, Bridges C, Cox N. Inativated Influenza Vaccines. In Plotkin SA OW, editor. VACCINES, Philadelphia: Saunders, 2004: 339-38880 - 120 nmAntigene interneNucleocapsida: Nucleoproteina (Ag specific de tip) Matrix protein (ex: M1, M2)Genom: 8 fragmente ARNHemaglutinina (HA) H1-H16

    Neuraminidaza (NA) N1-N9

    Anvelopa: dublu strat lipidicAnticorpiprotectoriAntigene de suprafa

    *Virus ARN cu anvelopa; forma sferica sau filamentoasaRaport N/H=1/4; 135 combinatii teoretic posibileH cel mai important Ag; - favorizeaza pentrarea virusului in celula (rol de receptor viral, asigurand fixarea virusului la nivelul recep. celulei gazdaN eliberarea si detasarea particulelor virale nou-formate de la suprafata cel. epiteliale respiratorii; - favorizeaza diseminarea infectiei in profunzimea tractului respirator; - tinta importanta pentru terapia antivirala. Influenza viruses belong to the Orthomyxoviridae family and are classified into three distinct types, influenza A, influenza B, and influenza C virus, on the basis of major antigenic differences. In addition, there are significant differences in genetic organization, structure, host range, epidemiology, and clinical characteristics between the three influenza virus types. The morphologic characteristics of all influenza virus types, subtypes, and strains are similar. Electron microscopic studies estimate their size to be 80 to 120 nm in diameter and show them to be enveloped viruses covered with surface projections or spikes. They may exist as spherical or elongated filamentous particles as well. Eight structural proteins have been identified in influenza A viruses. The surface spikes are glycoproteins that possess either hemagglutinin (HA) or neuraminidase (NA) activity. Each rod-shaped HA spike measures approximately 4 nm in diameter by 14 nm in length. They can be removed from the intact virion by sodium dodecyl sulfate, by bromelain, or by chymotrypsin. Each spike is a trimer composed of three HA polypeptides, each with a molecular weight of 75,000 to 80,000, resulting in a trimer with a molecular weight of approximately 224,640. The HA is synthesized as a monomer (HA0), which is cleaved by host-cell proteases into HA1 and HA2 components that remain linked together. Antigenic sites and sites for binding to cells are located in the globular head of the molecule.The viral NA is an enzyme that catalyzes the removal of terminal sialic acids (N-acetyl neuraminic acid) from sialic acidcontaining glycoproteins. The NA spike is shaped like a mushroom rather than a rod and has a molecular weight of 240,000. The intact NA consists of a tetramer of NA polypeptides, each with a molecular weight of 58,000. As in HA, the antigenic sites and the enzyme active site are located in the mushroom-shaped head.

    (2). Mandell, Bennett, & Dolin: Principles and Practice of Infectious Diseases, 6th ed., Chapter 162 - Influenza Virus accessed on April 05th 2006

  • Virusuri gripaleOm

    H1, H2 i H3N1 i N2Transmitere aerianAnimale

    H1 - H16N1 - N9Transmitere mai ales fecal-oral


  • Virusul gripal A vs BDe ce nu avem pandemii cu virusul gripal B?Virusul gripal A - cel mai rspndit la om, psri i animale

    Are mare variabilitate genetic

    Are numeroase subtipuri: 16 HA, 9 NA

    Virulen mare

    Responsabil de marile epidemii / pandemii

    Afecteaz toate grupele de vrst

    Virusul gripal B - afecteaz predominant omul

    Variabilitate genetic redus

    Nu exist subtipuri

    Forme clinice mai puin severe

    Produce rareori epidemii

    Afecteaz predominant copiii

    *Influenza type A infects multiple species. Several human influenza strains are type A while all avian strains are type A. They are considered the most virulent group, although not all strains cause clinical disease. Type A influenza viruses are classified into subtypes based on two surface antigens known as hemagglutinin (H) and neuraminidase (N), sometimes also referred to as HA and NA respectively.

    There are 15 different HA and 9 different NA antigens in influenza A. All of these different antigens can be found in aquatic birds. The HA is the hemagglutinin antigen and it functions as the site for attachment to host cells. The NA or neuraminidase antigen serves to remove neuraminic acid from mucin allowing the virus to be released from the cell.

  • Variabilitatea geneticInteligena virusurilor gripale Antigene de suprafa modificate Potenial ameninare Drift antigenic (modificri minore )

    Gripa sezonier

    Shift antigenic (modificri majore)Emergena tulpinii pandemice Gripa pandemic

    *Titrul Ac scade in timp (persista IgG, dar rolul lor protectiv este mai mic decat al IgA).

    Ag shift occurs in two ways: Sudden adaptive change during replication of a normal virus OR From an exchange of genes between human strain of an influenza A virus and an animal strain

    OK, lets see if you remember what Ive told you about seasonal influenza and influenza pandemic. Do you still remember the surface antigens of influenza viruses?We have learnt that changes in the surface antigens, whether they be minor or major, will cause different levels of threat to our health and lives. Minor changes in the antigen will bring about seasonal influenza, and major changes in the antigen mean that humans have little if not no immunity against the virus. Such a new virus will spread with a greater speed and extensiveness than seasonal influenza does. The emergence of such a novel strain could mark the start of an influenza pandemic.Be it seasonal influenza, avian influenza or influenza pandemic, the key to ward off the disease is to follow good personal safety measures that protects you from the infection.So, what are these measures?

  • De unde vin noi HA i NA?


  • Mutaii sau schimb de material genetic ntre virusuri infectnd aceeai celul

  • Pandemia pan - tot, demos - "popor" Definiie:

    Pandemia este o epidemie care afecteaz un procent mare din populaie, din toate zonele lumii

    Caracteristici:Sunt produse numai de virusul gripal ASunt declanate de un antigenic shiftDebuteaz de obicei ca o zoonoz, extinzndu-se apoi la omMajoritatea populaiei este naiv (nepregtit) imunologic Se extinde rapid pe tot globulAfecteaz 25-50% din populaia mondialAfecteaz adulii sntoiDetermin o mortalitate nalt


  • *1918-1919 pandemic probably caused 20-50 million deaths the single most devastating disease outbreak in human history

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    * H3N2 genotype most prevalent but occasionally a season is dominated by H1N1 (the virus that causedthe 1918 pandemic).

    Incepand cu 1968, epidemiile de gripa sezoniera au fost dominate de virusuri subtip H3N2Caracterizata de evolutie antigenica punctiformUneori, au loc evenimente tip reasortare genetica intre tulpinile circulante

  • *

  • Circulaia virusului gripal A n ultimul secol1918195719681977Gripa SpaniolGripa AsiaticGripaHong KongH1N1H2N2H3N2H1N1?

    Drift Ag

    Shift Ag

  • H5N1-risc de pandemie


  • FAZELE PANDEMIEI DE GRIP www.who.intRISCUL de pandemie H5N1Transmitere interuman ?Posibil... dar neconfirmat...

  • Noul virus gripal A 2009