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Amman May, 5, 2009 Influenza A Viruses Mohammad Q Al-Natour, DVM, MPH, Ph. D Amman May, 5, 2009 Influenza A Viruses Mohammad Q Al-Natour, DVM, MPH, Ph. D Associate Prof. of Avian Diseases [email protected] com & [email protected] edu. jo Mobile: 0795 -134 -993 Avian Diseases Research Lab. Department of Pathology & Animal Health Faculty of Veterinary Medicine Jordan University of Science and Technology Irbid - Jordan

Key properties of type A influenza virus Multiple serotypes n Wide spectrum of pathogenicity Key properties of type A influenza virus Multiple serotypes n Wide spectrum of pathogenicity n Wide host range n Global ? n International trade & of economic n n n significance? ? Incubation period (H 1 N 1): 1 -3 days in pigs Pigs excreting virus within 24 hrs of infection Virus shedding for 7 -10 days Pigs recover within 5 -7 days

Orthomyxoviridae Humans Horses Influenza virus A Cats Pigs Birds Marine mammals Influenza virus B Orthomyxoviridae Humans Horses Influenza virus A Cats Pigs Birds Marine mammals Influenza virus B Influenza virus C Humans Pigs Humans

Orthomyxoviridae A. I. Virus Single stranded RNA –ve n Segmented: 8 genes cod for Orthomyxoviridae A. I. Virus Single stranded RNA –ve n Segmented: 8 genes cod for 10 proteins n Two glycoprotein surface projection: - Haemagglutinin (HA): H 1 -H 16 - Neuraminidase (NA): N 1 -N 9 n Enveloped (20% lipid): Sensitive to heat, dryness and normal disinfectants n Antigenic types A, B, C n Pathogenicity vary n

Haemagglutinin and Neuraminidase sialic acid on receptor HA receptor binding site variable loops N Haemagglutinin and Neuraminidase sialic acid on receptor HA receptor binding site variable loops N active site variable loops

Cleavage of HA binds receptor HA 0 penetrates cell Clara (mucus), extracellular, serum, bacterial Cleavage of HA binds receptor HA 0 penetrates cell Clara (mucus), extracellular, serum, bacterial proteases binds receptor HA 1 HA 2

HA cleavage and virulence May ‘ 94 -> June ‘ 94 PQ--RETR Dec ‘ HA cleavage and virulence May ‘ 94 -> June ‘ 94 PQ--RETR Dec ‘ 94 -> P Q R K T R Jan ‘ 95 low cleavability low virulence respiratory infection high cleavability high virulence systemic infecton ?

Influenza virus replication HA cleaved by proteases HA binds to receptor virus buds lowered Influenza virus replication HA cleaved by proteases HA binds to receptor virus buds lowered p. H, HA fuses membranes virus in phagolysosome RNA released N releases virus

Infection cycle of influenza 1. 2. 3. 4. 5. 6. 7. Binding of virus Infection cycle of influenza 1. 2. 3. 4. 5. 6. 7. Binding of virus to cell Cell engulfs virus via endocytosis Membrane of virus fuses with endosome; RNA released into cell Viral polymerase produces m. RNA from viral RNA Protein, new RNA produced Self-assembly produces virions Virions bud off cell membrane

Infection cycle: Binding and endocytosis n HA contains receptor binding site for virus – Infection cycle: Binding and endocytosis n HA contains receptor binding site for virus – Binds to sialic acid residue on cell surface glycoprotein n Binding triggers receptormediated endocytosis – Virus is taken into endosome – Low p. H of endosome causes fusion of viral and endosome membranes

Type A Influenza Surface Antigens Surface Antigen Subtype 16 Type A Influenza Surface Antigens Surface Antigen Subtype 16

Reassortment Reassortment

Evolution and Spread of flu viruses pigs poultry aquatic birds fecal/oral All HA and Evolution and Spread of flu viruses pigs poultry aquatic birds fecal/oral All HA and N serotypes humans H 1 N 1 H 3 N 2 H 1 N 1 H 2 N 2 H 3 N 2 (H 5 N 1, H 9 N 2) horses H 3 N 8 H 7 N 7 respiratory

The avian HK viruses The avian HK viruses

Swayne, D. E. Epidemiology of Avian Influenza in Agricultural and Other Man-Made Systems. In: Swayne, D. E. Epidemiology of Avian Influenza in Agricultural and Other Man-Made Systems. In: Avian Influenza. Wylie-Blackwell, in press, March, 2008.

Swayne, D. E. Understanding the ecology and epidemiology of avian influenza viruses: implications for Swayne, D. E. Understanding the ecology and epidemiology of avian influenza viruses: implications for zoonotic potential. In: Emerging Infectious Diseases of Animals. pp. 101 -130, ASM Press, 2000.

Generation of Pandemic Influenza Strain Avian virus Avian reassortant virus Avian virus Human virus Generation of Pandemic Influenza Strain Avian virus Avian reassortant virus Avian virus Human virus Reassortment in swine CDC Reassortment in humans Avian-human pandemic reassortant virus 19

Influenza A(H 1 N 1) - update n n n 4 May 2009 -- Influenza A(H 1 N 1) - update n n n 4 May 2009 -- As of 06: 00 GMT, 4 May 2009, 20 countries have officially reported 985 cases of influenza A (H 1 N 1) infection. Mexico has reported 590 laboratory confirmed human cases of infection, including 25 deaths. The higher number of cases from Mexico reflects ongoing testing of previously collected specimens. The United States has reported 226 laboratory confirmed human cases, including one death. The following countries have reported laboratory confirmed cases with no deaths - Austria (1), Canada (85), China, Hong Kong Special Administrative Region (1), Costa Rica (1), Colombia (1), Denmark (1), El Salvador (2), France (2), Germany (8), Ireland (1), Israel (3), Italy (1), Netherlands (1), New Zealand (4), Republic of Korea (1), Spain (40), Switzerland (1) and the United Kingdom (15).

Influenza A(H 1 N 1) - update n There is no risk of infection Influenza A(H 1 N 1) - update n There is no risk of infection from this virus from consumption of well-cooked pork and pork products. n It is considered prudent for people who are ill to delay international travel and for people developing symptoms following international travel to seek medical attention, in line with guidance from national authorities. Individuals are advised to wash hands thoroughly with soap and water on a regular basis and should seek medical attention if they develop any symptoms of influenza-like illness. WHO advises no restriction of regular travel or closure of borders. n

The A/H 1 N 1 situation needs to be carefully monitored. Influenza viruses, whether The A/H 1 N 1 situation needs to be carefully monitored. Influenza viruses, whether in humans or among animals, are constantly evolving genetically, along with changes in their ability to cause morbidity and mortality in humans or animals. Therefore the current A/H 1 N 1 situation should be carefully monitored as many of the virus characteristics and developments are still unknown, Domenech said.

n Surveillance for porcine respiratory disease should be intensified and all cases of porcine n Surveillance for porcine respiratory disease should be intensified and all cases of porcine respiratory syndrome are recommended to be immediately reported to veterinary authorities. It is also recommended to inform OIE and FAO about any occurrence of outbreaks of the new A/H 1 N 1 Influenza virus in pigs. n Strict biosecurity measures including restriction of movements of pigs, goods and people should be applied on all farms or holdings with swine showing signs of clinical respiratory illness until diagnosis of the illness has been made.

n Where A/H 1 N 1 influenza is confirmed, movement restrictions should be in n Where A/H 1 N 1 influenza is confirmed, movement restrictions should be in force for seven days after the last animal has recovered. Governments are requested to provide full support in improving biosecurity measures particularly to small and medium pig farmers. n Persons who work directly with swine should be urged not to go to work if they have any signs of respiratory disease, fever or any influenza-like illness. Animal handlers and veterinarians should wear protective clothing to minimize the risk of being infected. n FAO stressed that there is absolutely no need to slaughter animals in view of preventing circulation of the A/H 1 N 1 virus. n The agency emphasized that the A/H 1 N 1 virus cannot be transmitted to humans by pork and pork products. Pork and pork products, handled in accordance with good hygienic practices recommended by the FAO/WHO Codex Alimentarius Commission and the OIE, will not be a source of infection.

Thank You n Avian Flu in Arabic Language n n Prof. Abo-Shehada Dr. Al-Natour Thank You n Avian Flu in Arabic Language n n Prof. Abo-Shehada Dr. Al-Natour n 2 nd Edition, 2007 M. N. Abo-Shehada M. Q. Al-Natour 2007