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Avian Influenza Virus

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Avian Influenza Virus

  1. 1. AIV
  2. 2. Influenza Virus Classification Influenza virus is classified into 3 types; A, B and C. Type A – Avian, human, mammalian – Pandemics Type B – Human, causes epidemics disease similar to type A Type C – Humans, swine – 7 segments – lacks NA but contains esterase – Mild infections
  3. 3. Avian Influenza Virus (AIV) The avian influenza (AI) virus is type A influenza isolated from and adapted to an avian host.
  4. 4. Cont. …  Type A influenza belongs to the orthomyxovirdae virus family, is enveloped, and is pleiomorphic with a size ranging from 80–120 nm.  Type A influenza strains are classified by the serological subtypes of the primary viral surface proteins – Hemagglutinin (HA) – Neuraminidase (NA)
  5. 5. Cont. …  The HA has 16 subtypes (H1–H16) and contains neutralizing epitopes.  Antibodies against the NA are not neutralizing, and there are 9 neuraminidase or “N” subtypes.
  6. 6. Cont. …  The “H” and N subtypes seem to be able to be assorted into any combination, and many of the 144 possible combinations have been found in natural reservoir species, although some combinations are more common than others.
  7. 7. Cont. …  All 16 HA subtypes have been found in ducks, gulls, or shorebirds, the natural reservoir host species of the virus.
  8. 8. Cont. … However, in these species certain subtypes are more common than others; for example: 1. H3, H4, and H6 are most common in ducks in North America 2. H1 and H3 in swine 3. H3 in horses 4. H5 and H7 in chickens.
  9. 9. AIV Molecular Biology  The genome of type A influenza is single-stranded, negative-sense RNA and contains 8 genome segments that encode 10 or 11 proteins depending on the isolate.
  10. 10. Segment Name Type Function 1 PB1 Polymerase complex • Transcriptase 2 PB2 Polymerase complex • Endonuclease 3 PB3 Polymerase complex 1- RNA replication 2- proteolytic activities 4 HA Membrane glycoprotein 1. Attachment to sialyoligosacharide cell receptor 2. Envelope fusion 3. Neutralizing AB production 5 NP Major structure RNA 1. Transport of RNP 2. Antigen target for CTL 6 NA Membrane glycoprotein 1. Cell receptor destroying enzyme (sialic acid) that elute the virus 7 Matrix – 1 (M1) Non glycosylated structure protein beneath virus envelope Virus budding 8 Non structural – 1 (NS1) RNA binding protein Inhibit processing of cellular matrix Non structural – 2 (NS2) Nuclear export protein Nuclear export viral RNA Genome Segments Functions
  11. 11. AIV Replication Cycle  The virus replication cycle, which takes place in the nucleus, has been well described, although details on the functions of some proteins remain unclear.
  12. 12. Molecular Biology Pathogenicity  In gallinaceous birds (i.e., chickens, turkeys, and quail), the HA protein is the primary mediator of pathogenicity.  Depending on which proteolytic enzyme recognizes the HA cleavage site, virus pathogenecity would be determined. 1. Highly pathogenic • Requires any proteolytic (protease) enzyme. • Cause systemic infection. 2. Low pathogenic • Requires trypsin enzyme. • Cause restricted to the respiratory and enteric tracts.
  13. 13. Cont. …  Additionally, relatively little is known about the molecular determinants of pathogenicity for type A influenza in hosts other than gallinaceous birds, although there is increasing evidence for the importance of the NS1 protein.
  14. 14. Molecular Biology Mutation  Typical of RNA viruses, type A influenza is able to generate a high degree of genetic diversity by mutation within genes.  In addition to a high mutation rate, reassortment (which is the mixing of gene segments between different strains and lineages during concomitant infection) is an additional mechanism for generating variability in the influenza genome.
  15. 15. Cont. …  Certainly, the high genetic variability of the type A influenza virus contributes to the high adaptability of the virus and its ability to evade the immune system by antigenic drift (mutation) and antigenic shift (reassortment of the hemagglutinin).
  16. 16. Host Range  Although the natural host reservoir species for the AI virus is waterfowl, particularly ducks.  On rare occasions, the virus has been transmitted to a non natural host species including other avian species and numerous mammalian species.  On even rarer occasions a virus lineage may become adapted to, and established in, the new host species (i.e., swine H1N1, equine H3N8).
  17. 17. Cont. …  It is very important to recognize that isolation of a virus from a particular species does not indicate that the host is a natural host or reservoir species.  Many avian species are not natural hosts, including chickens and turkeys.  However, in cases where an AI virus becomes adapted to these species, they may serve as a reservoir.
  18. 18. AIV Pathogenicity In gallinaceous birds (i.e., chickens and turkeys), AI viruses are classified as being: 1. Highly pathogenic AI (HPAI) virus. 2. Low pathogenic AI (LPAI) virus.
  19. 19. Cont. … Molecular criteria have been established by the World Organization for Animal Health (formerly the OIE) for the identification of the HPAI virus based on the protein sequence of the HA proteolytic cleavage site, in vivo testing is more reliable for clinical classification.
  20. 20. Cont. …
  21. 21. Cont. …  Biologically, the difference between HPAI and LPAI is that HPAI is a systemic infection and LPAI remains localized to the respiratory and intestinal tracts.  For unknown reasons, all HPAI viruses have been either H5 or H7 HA subtypes.
  22. 22. Cont. … Cleavage site of the HA Wild type CCT CAA AGA GAG AGA AGA AGA AAA AGA AGA GGA CTA TTT Pro Gin Arg Glu Arg Arg Arg Lys Lys Arg Gly Leu Phe Modified type CCT CAA AGA GAG AGA AGA --- --- --- --- GGA CTA TTT Pro Gin Arg Glu Arg Arg --- --- --- --- Gly Leu Phe
  23. 23. Cont. … As a result of such lowered pathogenecity, 1. Grows on chicken egg embryo and tissue culture. 2. Failed to kill chicken embryo. 3. Failed to produce plaques in tissue culture in the absence of trypsin.
  24. 24. Cont. …  AI virus isolate is classified as being HPAI if it: 1. kills at least 75% of susceptible 4 to 6 week old chickens within 10 days post inoculation by the intravenous route. 2. Some isolates will cause 100% mortality by 36–48 hours post inoculation.  All other isolates are considered to be LPAI viruses.
  25. 25. Cont. … LPAI HPAI Respiratory – Intestine Systemic Trypsine Protease Morbidity Mortality Any HA H5 – H7
  26. 26. Cont. …  The generation of HPAI viruses appears to be a phenomenon associated with adaptation of LPAI viruses to chickens or turkeys.
  27. 27. Cont. …  AI viruses from waterfowl are LPAI for gallinaceous birds, and some waterfowl adapted isolates will not even replicate in chickens.  However, once an H5 or H7 LPAI virus has been transmitted to chickens or turkeys, it has the potential to become an HPAI virus, although most strains remain low pathogenic.
  28. 28. Cont. …  In some cases, the mutation from LPAI to HPAI has occurred within weeks of virus introduction into poultry (i.e., Chile 2002 and British Columbia 2004) and in other cases has taken from months to years (i.e., Pennsylvania 1983 and Mexico 1994).

Notas do Editor

  • Shorebirds الطيور الساحلية
  • Shorebirds الطيور الساحلية
  • Reverse-transcribing RNA viruses use the enzyme to reverse-transcribe their RNA genomes into DNA
    Endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain. Some, such as Deoxyribonuclease I, cut DNA relatively nonspecifically (without regard to sequence), while many, typically called restriction endonucleases or restriction enzymes, cleave only at very specific nucleotide sequences.

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