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

Key properties of type A influenza virus Multiple serotypes Multiple serotypes Wide spectrum of pathogenicity Wide spectrum of pathogenicity Wide host range Wide host range Global ? Global ? International trade & of economic significance?? International trade & of economic significance?? Incubation period (H1N1): 1-3 days in pigs Incubation period (H1N1): 1-3 days in pigs Pigs excreting virus within 24 hrs of infection Pigs excreting virus within 24 hrs of infection Virus shedding for 7-10 days Virus shedding for 7-10 days Pigs recover within 5-7 days Pigs recover within 5-7 days

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

Orthomyxoviridae A.I. Virus Single stranded RNA –ve Single stranded RNA –ve Segmented: 8 genes cod for 10 proteins Segmented: 8 genes cod for 10 proteins Two glycoprotein surface projection: Two glycoprotein surface projection: - Haemagglutinin (HA): H1-H16 - Haemagglutinin (HA): H1-H16 - Neuraminidase (NA): N1-N9 - Neuraminidase (NA): N1-N9 Enveloped (20% lipid): Sensitive to heat, dryness and normal disinfectants Enveloped (20% lipid): Sensitive to heat, dryness and normal disinfectants Antigenic types A, B, C Antigenic types A, B, C Pathogenicity vary Pathogenicity vary

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

Cleavage of HA Clara (mucus), extracellular, serum, bacterial proteases HA0 HA1 HA2 binds receptor binds receptor penetrates cell

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

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

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

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

Type A Influenza Surface Antigens Surface Antigen Subtype 16

Reassortment

Evolution and Spread of flu viruses aquatic birds poultry pigs humans horses fecal/oral respiratory All HA and N serotypes H3N8 H7N7 H1N1 H3N2 H1N1 H2N2 H3N2 (H5N1, H9N2)

The avian HK viruses

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 zoonotic potential. In: Emerging Infectious Diseases of Animals. pp , ASM Press, 2000.

CDC19 Avian-human pandemic reassortant virus Avian virusHuman virus virus Avian reassortant virus Avian virus Reassortment in swine Reassortment in humans Generation of Pandemic Influenza Strain

Influenza A(H1N1) - update 4 May As of 06:00 GMT, 4 May 2009, 20 countries have officially reported 985 cases of influenza A (H1N1) infection. 4 May As of 06:00 GMT, 4 May 2009, 20 countries have officially reported 985 cases of influenza A (H1N1) 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. 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). 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(H1N1) - update There is no risk of infection from this virus from consumption of well-cooked pork and pork products. There is no risk of infection from this virus from consumption of well-cooked pork and pork products. 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. 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. WHO advises no restriction of regular travel or closure of borders.

The A/H1N1 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/H1N1 situation should be carefully monitored as many of the virus characteristics and developments are still unknown, Domenech said.

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/H1N1 Influenza virus in pigs. 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/H1N1 Influenza virus in pigs. 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. 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.

Where A/H1N1 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. Where A/H1N1 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. 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. 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. FAO stressed that there is absolutely no need to slaughter animals in view of preventing circulation of the A/H1N1 virus. FAO stressed that there is absolutely no need to slaughter animals in view of preventing circulation of the A/H1N1 virus. The agency emphasized that the A/H1N1 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. The agency emphasized that the A/H1N1 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 M. N. Abo-Shehada M. Q. Al-Natour 2007 Avian Flu in Arabic Language Avian Flu in Arabic Language Prof. Abo-Shehada Prof. Abo-Shehada Dr. Al-Natour Dr. Al-Natour 2 nd Edition, nd Edition, 2007