Influenza A Viruses Influenza A Viruses

Mohammad Q Al-NatourMohammad Q Al-Natour,, DVM, MPH, Ph.DDVM, MPH, Ph.D

Associate Prof. of Avian DiseasesAssociate Prof. of Avian Diseases

mqalnatour@yahoo.com & alnatour@just.edu.jomqalnatour@yahoo.com & alnatour@just.edu.jo

Mobile: 0795-134-993Mobile: 0795-134-993

Avian Diseases Research Lab.Avian Diseases Research Lab.

Department of Pathology & Animal HealthDepartment of Pathology & Animal Health

Faculty of Veterinary MedicineFaculty of Veterinary Medicine

Jordan University of Science and TechnologyJordan University of Science and Technology

Irbid - JordanIrbid - Jordan

AmmanAmmanMay, 5, 2009May, 5, 2009

Key properties of type A Key properties of type A influenza virusinfluenza virus

Multiple serotypesMultiple serotypes Wide spectrum of pathogenicityWide spectrum of pathogenicity Wide host rangeWide host range Global ?Global ? International trade & ofInternational trade & of economic economic

significance?? significance?? Incubation period (H1N1): 1-3 days in pigsIncubation period (H1N1): 1-3 days in pigs Pigs excreting virus within 24 hrs of infectionPigs excreting virus within 24 hrs of infection Virus shedding for 7-10 daysVirus shedding for 7-10 days Pigs recover within 5-7 days Pigs recover within 5-7 days

OrthomyxoviridaeOrthomyxoviridae

Influenza virus A

Influenza virus B

Influenza virus C

Humans

Horses

Pigs

Birds

Marine mammals

Humans

Humans

Pigs

Cats

OrthomyxoviridaeOrthomyxoviridaeA.I. VirusA.I. Virus

Single stranded RNA –ve Single stranded RNA –ve Segmented: 8 genes cod for 10 proteinsSegmented: 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): Enveloped (20% lipid): SensitiveSensitive to heat, dryness and to heat, dryness and

normal disinfectantsnormal disinfectants Antigenic types A, B, CAntigenic types A, B, C Pathogenicity varyPathogenicity vary

Haemagglutinin and NeuraminidaseHaemagglutinin and Neuraminidase

receptorbindingsite

active site

variableloops

variableloops

HA N

sialic acidon receptor

Cleavage of HACleavage of HA

Clara (mucus),extracellular,serum,bacterialproteases

HA0

HA1

HA2

bindsreceptor binds

receptorpenetratescell

HA cleavage and virulenceHA cleavage and virulence

May ‘94 ->June ‘94

Dec ‘94 ->Jan ‘95

P Q - - R E T R lowcleavability

lowvirulence

P Q R K R K T R highcleavability

highvirulence

systemicinfecton

respiratoryinfection

?

Influenza virus replicationInfluenza virus replication

HA cleavedbyproteases HA binds to

receptor

virus inphagolysosome

loweredpH, HAfusesmembranes

RNAreleased

virusbuds

N releasesvirus

Infection cycle of influenzaInfection cycle of influenza

1.1. Binding of virus to cellBinding of virus to cell

2.2. Cell engulfs virus via Cell engulfs virus via endocytosisendocytosis

3.3. Membrane of virus fuses with Membrane of virus fuses with endosome; RNA released into endosome; RNA released into cellcell

4.4. Viral polymerase produces Viral polymerase produces mRNA from viral RNAmRNA from viral RNA

5.5. Protein, new RNA producedProtein, new RNA produced

6.6. Self-assembly produces virionsSelf-assembly produces virions

7.7. Virions bud off cell membraneVirions bud off cell membrane

Infection cycle: Infection cycle: Binding and endocytosisBinding and endocytosis

HA contains receptor binding HA contains receptor binding site for virussite for virus– Binds to sialic acid residue on Binds to sialic acid residue on

cell surface glycoproteincell surface glycoprotein

Binding triggers receptor-Binding triggers receptor-mediated endocytosismediated endocytosis– Virus is taken into endosomeVirus is taken into endosome

– Low pH of endosome causes Low pH of endosome causes fusion of viral and endosome fusion of viral and endosome membranesmembranes

Type A Influenza Surface AntigensType A Influenza Surface AntigensSurface Antigen Subtype

Hemagglutinin: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Human Equine Swine Avian Neuraminidase: 1 2 3 4 5 6 7 8 9 Human Equine Swine Avian

16

ReassortmentReassortment

Evolution and Spread of flu virusesEvolution and Spread of flu viruses

aquatic birds

poultry

pigs

humans

horsesfecal/oral

respiratory

All HA and N serotypes

H3N8

H7N7

H1N1H3N2

H1N1H2N2H3N2(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. 101-130, ASM Press, 2000.

CDC 19

Avian-human pandemic reassortant

virus

Avianvirus

HumaHumann

virusvirus

Avian reassortant

virus

Avianvirus

Reassortment in swine

Reassortment in humans

Generation of Pandemic Influenza StrainGeneration of Pandemic Influenza Strain

Influenza A(H1N1) - update Influenza A(H1N1) - update 4 May 2009 -- As of 06:00 GMT, 4 May 2009, 20 countries have 4 May 2009 -- As of 06:00 GMT, 4 May 2009, 20 countries have

officially reported 985 cases of influenza A (H1N1) infection.officially reported 985 cases of influenza A (H1N1) infection. Mexico has reported 590 laboratory confirmed human cases of infection, Mexico has reported 590 laboratory confirmed human cases of infection,

including 25 deaths. The higher number of cases from Mexico reflects including 25 deaths. The higher number of cases from Mexico reflects ongoing testing of previously collected specimens. The United States has ongoing testing of previously collected specimens. The United States has reported 226 laboratory confirmed human cases, including one death.reported 226 laboratory confirmed human cases, including one death.

The following countries have reported laboratory confirmed The following countries have reported laboratory confirmed cases with no deaths - Austria (1), Canada (85), China, Hong cases with no deaths - Austria (1), Canada (85), China, Hong Kong Special Administrative Region (1), Costa Rica (1), Kong Special Administrative Region (1), Costa Rica (1), Colombia (1), Denmark (1), El Salvador (2), France (2), Colombia (1), Denmark (1), El Salvador (2), France (2), Germany (8), Ireland (1), Israel (3), Italy (1), Netherlands Germany (8), Ireland (1), Israel (3), Italy (1), Netherlands (1), New Zealand (4), Republic of Korea (1), Spain (40), (1), New Zealand (4), Republic of Korea (1), Spain (40), Switzerland (1) and the United Kingdom (15). Switzerland (1) and the United Kingdom (15).

Influenza A(H1N1) - update Influenza A(H1N1) - update There is no risk of infection from this virus There is no risk of infection from this virus

from consumption of well-cooked pork and from consumption of well-cooked pork and pork products.pork products.

It is considered prudent for people who are ill to delay It is considered prudent for people who are ill to delay international travel and for people developing symptoms international travel and for people developing symptoms following international travel to seek medical attention, in following international travel to seek medical attention, in line with guidance from national authorities. line with guidance from national authorities. Individuals Individuals are advised to wash hands thoroughly with soap and water are advised to wash hands thoroughly with soap and water on a regular basis and should seek medical attention if they on a regular basis and should seek medical attention if they develop any symptoms of influenza-like illness. develop any symptoms of influenza-like illness.

WHO advises no restriction of regular travel or closure of WHO advises no restriction of regular travel or closure of borders. borders.

The A/H1N1 situation needs to be The A/H1N1 situation needs to be carefully monitored. carefully monitored.

Influenza viruses, whether in humans or Influenza viruses, whether in humans or among animals, are constantly evolving among animals, are constantly evolving genetically, along with changes in their genetically, along with changes in their

ability to cause morbidity and mortality in ability to cause morbidity and mortality in humans or animals. humans or animals. Therefore the current Therefore the current

A/H1N1 situation should be carefully A/H1N1 situation should be carefully monitored as many of the virus monitored as many of the virus

characteristics and developments are still characteristics and developments are still unknown, unknown, Domenech said.Domenech said.

Surveillance Surveillance for porcine respiratory disease should be for porcine respiratory disease should be intensified and all cases of porcine respiratory syndrome are intensified and all cases of porcine respiratory syndrome are recommended to be immediately reported to veterinary recommended to be immediately reported to veterinary authorities. It is also recommended to inform OIE and FAO authorities. It is also recommended to inform OIE and FAO about any occurrence of outbreaks of the new A/H1N1 about any occurrence of outbreaks of the new A/H1N1 Influenza virus in pigs.Influenza virus in pigs.

Strict biosecurity measures Strict biosecurity measures including restriction of movements including restriction of movements of pigs, goods and people should be applied on all farms or of pigs, goods and people should be applied on all farms or holdings with swine showing signs of clinical respiratory holdings with swine showing signs of clinical respiratory illness until diagnosis of the illness has been made.illness until diagnosis of the illness has been made.

Where A/H1N1 influenza is confirmed, Where A/H1N1 influenza is confirmed, movement restrictions should movement restrictions should be in force for seven days after the last animal has recovered. be in force for seven days after the last animal has recovered. Governments are requested to provide full support in improving Governments are requested to provide full support in improving biosecurity measures particularly to small and medium pig farmers.biosecurity measures particularly to small and medium pig farmers.

Persons who work directly with swine Persons who work directly with swine should be urged not to go to should be urged not to go to work if they have any signs of respiratory disease, fever or any work if they have any signs of respiratory disease, fever or any influenza-like illness. Animal handlers and veterinarians should wear influenza-like illness. Animal handlers and veterinarians should wear protective clothing to minimize the risk of being infected.protective clothing to minimize the risk of being infected.

FAO stressed that there is absolutely no need to slaughter animals FAO stressed that there is absolutely no need to slaughter animals in in view of preventing circulation of the A/H1N1 virus.view of preventing circulation of the A/H1N1 virus.

The agency emphasized that the A/H1N1 virus cannot be transmitted The agency emphasized that the A/H1N1 virus cannot be transmitted to humans by pork and pork products. Pork and pork products, to humans by pork and pork products. Pork and pork products, handled in accordance with good hygienic practices recommended by handled in accordance with good hygienic practices recommended by the FAO/WHO Codex Alimentarius Commission and the OIE, will the FAO/WHO Codex Alimentarius Commission and the OIE, will not be a source of infection. not be a source of infection.

Thank YouThank You

M. N. Abo-ShehadaM. N. Abo-ShehadaM. Q. Al-NatourM. Q. Al-Natour20072007

Avian Flu in Arabic Avian Flu in Arabic LanguageLanguage

Prof. Abo-Shehada Prof. Abo-Shehada Dr. Al-NatourDr. Al-Natour

22ndnd Edition, 2007 Edition, 2007