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Avian Influenza Viruses and its
      role in inter-species Transmission




                 Rokshana Parvin and T.W. Vahlenkamp




INSTITUT FÜR VIROLOGIE
Influenza virus

    Influenza viruses causes highly contagious respiratory
    disease with potentially fatal outcomes.

    Family: Orthomyxoviridae
    Three main types
        Type A
           Multiple species
         Type B
           Humans
         Type C
           Humans and swine



                                      http://www.uct.ac.za/depts/mmi/stannard/fluvirus.html

INSTITUT FÜR VIROLOGIE
Influenza virus genome
     The influenza A genome consists of eight single-stranded negative-
     sense RNA molecules encoded 10 proteins within viral envelope

                           HA - hemagglutinin

                                     NA - neuraminidase                   HA
                                                                          NA
                                                                          M
                                 helical nucleocapsid (RNA plus           NS
                                 NP protein)                              NP
                                                                          PA
                                     lipid bilayer membrane               PB1
                                                                          PB2
                                     polymerase complex



                                M1 protein

INSTITUT FÜR VIROLOGIE
Influenza virus Type A
     Influenza A viruses are further classified into subtypes based on the
       antigenicity of their surface glycoproteins (HA & NA )

       Hemagglutinin (HA)                   Neuraminidase (NA)
       H1, H2, H3, H4, H5, H6, H7, H8,      N1, N2, N3, N4, N5, N6, N7, N8,
       H9, H10, H11, H12, H13, H14,         N9
       H15, H16
          So far at least 84 serotypes (HA &NA combination) are found in
                                      resivour

     Infect multiple species
      Humans
      Birds (wild birds, domestic poultry)
      Other animals: pigs, horses, dogs, marine mammals (seals,
        whales)



INSTITUT FÜR VIROLOGIE
H5




                                           H5, H7, H9
                                                             H3, H7


                                HA 1-16
                                NA 1-9
   H4, H7, H13




                 H1 - H3                  H1 - H3            H3, H7
                                          H5, H7, H9    H5

INSTITUT FÜR VIROLOGIE
How they transmitted ??????????????


         The virus is contracted through
          Contact with saliva, nasal secretions and feces of the wild birds.
          Contaminated surfaces or materials.
          Contaminated water
         * Direct or indirect contact




INSTITUT FÜR VIROLOGIE
True influenza
                    influenza virus A or influenza virus B




       Febrile respiratory disease with systemic symptoms
       caused by a variety of other organisms often called „flu‟




INSTITUT FÜR VIROLOGIE
Influenza descriptions

     Influenza name Strain                Host affected    Outbreak year
     Seasonal Flu       H3, H1            humans           yearly
     Spanish Flu        H1N1              humans           1918
     Asian Flu          H2N2              humans           1957
     Hong Kong Flu      H3N2              humans           1968, 1970-72
     bird flu           H5N1              Poultry,         1997,
                                          (endemic in      2003………..
                                          avian), human,
                                          & cat
     Swine flu          H1N1              Humans, swine    2009
                 *   H1N2 is currently endemic in humans and pigs




INSTITUT FÜR VIROLOGIE
Bird Flu:
                   H5N1, H7N7,H9N2…




INSTITUT FÜR VIROLOGIE
HPAI                                  LPAI
                   H5, H7                                H9, H7
                   H5N1                                  H9N2

Highly pathogenic viruses result in high   Low pathogenicity viruses also cause
death rates (up to 100% mortality within   outbreaks in poultry but are not
48 hours) in some poultry species          generally associated with severe clinical
                                           disease




INSTITUT FÜR VIROLOGIE
transmitted to poultry




                                                       LPAI virus circulates in
    Natural reservoir of
                                                       poultry with mild disease
    LPAI (H9, H5, H7) virus




           LPAI Virus Mutates to
           HPAI with severe disease

INSTITUT FÜR VIROLOGIE
INSTITUT FÜR VIROLOGIE
• The current outbreaks of highly pathogenic avian
       influenza, which began in South-East Asia in mid-2003,
       are the largest and most severe on record

     • Never before in the history of this disease have so many
       countries been simultaneously affected, resulting in the
       loss of so many birds




INSTITUT FÜR VIROLOGIE
Outbreaks map of HPAI H5N1 in
             poultry (2003 – March 2012)




                                       ≥ 100 outbreaks
                                       ≥ 10 outbreaks
                                       ≥ 1 outbreaks


INSTITUT FÜR VIROLOGIE
Bird flu: Why is there a risk for humans?

     Role of pigs as an intermediate host




INSTITUT FÜR VIROLOGIE
Differences between Pandemics and
                     Epidemics

      Pandemics are different from seasonal outbreaks or
       “epidemics” of influenza

      Seasonal outbreaks are caused by subtypes of influenza
       viruses that are already in existence among people

      Pandemic outbreaks are caused by new subtypes or by
       subtypes that have never circulated among people or
       that have not circulated among people for a long time




INSTITUT FÜR VIROLOGIE
Seasonal Epidemics vs. Pandemics
          Seasonal Influenza          Influenza Pandemics

         – A public health problem    – Appear in the human
           each year                    population rarely and
                                        unpredictably

         – Usually some immunity
           built up from previous     – Human population lacks
           exposures to the same        any immunity
           subtype


         – Infants and elderly most   – All age groups, including
           at risk                      healthy young adults




INSTITUT FÜR VIROLOGIE
If a new subtype of influenza A virus is introduced into
      the human population, most people have little or no
      protection against the new virus, and if the virus can
      spread easily from person to person, a PANDEMIC
      (worldwide spread) may occur




INSTITUT FÜR VIROLOGIE
Prerequisites for pandemic influenza

           A new influenza virus emerges to which
           the general population has little/no
           immunity


            The new virus must be able to replicate
            in humans and cause disease

                The new virus must be efficiently
             transmitted from one human to another


      Ingredients for a pandemic are abundantly available

INSTITUT FÜR VIROLOGIE
Influenza A viruses are renowned for their rapid
            evolution in aberrant hosts including humans




    Antigenic drift occurs when single   Antigenic shift takes place when two
    nucleotides are replaced over time   different viruses infect the same cell and
    through mutations                    new viral particles are created with new
                                         combinations or assortments of the 8
                                         influenza molecules


INSTITUT FÜR VIROLOGIE
INSTITUT FÜR VIROLOGIE
Antigenic
                         shift




     Sick Pig with both Strands of Influenza


INSTITUT FÜR VIROLOGIE
1st pandemics of 21th century
     Pandemic      Year      Influenza virus   People infected   Estimated deaths
                             type                                worldwide

     Swine flu     2009–     Pandemic          > 622,482 (lab-   14,286 (lab-confirmed;
                   2010      H1N1              confirmed)        ECDC
                                                                 18,036 (lab-
                                                                 confirmed;WHO)



     The pandemic that began in March 2009 was caused by an H1N1
     influenza A virus that represents a quadruple reassortment of two swine
     strains, one human strain, and one avian strain of influenza; the largest
     proportion of genes came from swine influenza viruses.




INSTITUT FÜR VIROLOGIE
History of Reassortment Events in the
           Evolution of Influenza A H1N1/09




                                   H1N1/ 09

INSTITUT FÜR VIROLOGIE
INSTITUT FÜR VIROLOGIE
20th century flu pandemics

            Spanish flu                  Asian flu            Hong Kong Flu




       Emergency military hospital   Children's ward during   Hong Kong Flu Pandemic
       during Spanish flu pandemic   Asian flu pandemic       (1968,1970-1972)
       (1918)                        (1957)


           A(H1N1)                        A(H2N2)                  A(H3N2)
        20-40 m deaths                  1-4 m deaths              1-4 m deaths




INSTITUT FÜR VIROLOGIE
INSTITUT FÜR VIROLOGIE
Now literature says…
       Bird flu can transmitted directly from birds to humans




INSTITUT FÜR VIROLOGIE
Possible mechanisms for the generation of
                 pandemic influenza viruses

INSTITUT FÜR VIROLOGIE
Current situation




INSTITUT FÜR VIROLOGIE
INSTITUT FÜR VIROLOGIE
INSTITUT FÜR VIROLOGIE
http://www.who.int/csr/don/2012_04_12/en/index.html



INSTITUT FÜR VIROLOGIE
http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/gr
                         aph_avian_influenza/graphs_HPAI_31_03_2012.pdf



INSTITUT FÜR VIROLOGIE
INSTITUT FÜR VIROLOGIE
http://www.fao.org/ag/againfo/programmes/en/empres/maps_cum_archive.html


INSTITUT FÜR VIROLOGIE
Next warning
                              ?




INSTITUT FÜR VIROLOGIE
INSTITUT FÜR VIROLOGIE
For your kind attention!!!!




INSTITUT FÜR VIROLOGIE
INSTITUT FÜR VIROLOGIE
INSTITUT FÜR VIROLOGIE

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Avian influenza virus and transmission

  • 1. Avian Influenza Viruses and its role in inter-species Transmission Rokshana Parvin and T.W. Vahlenkamp INSTITUT FÜR VIROLOGIE
  • 2. Influenza virus Influenza viruses causes highly contagious respiratory disease with potentially fatal outcomes. Family: Orthomyxoviridae Three main types  Type A Multiple species  Type B Humans  Type C Humans and swine http://www.uct.ac.za/depts/mmi/stannard/fluvirus.html INSTITUT FÜR VIROLOGIE
  • 3. Influenza virus genome The influenza A genome consists of eight single-stranded negative- sense RNA molecules encoded 10 proteins within viral envelope HA - hemagglutinin NA - neuraminidase HA NA M helical nucleocapsid (RNA plus NS NP protein) NP PA lipid bilayer membrane PB1 PB2 polymerase complex M1 protein INSTITUT FÜR VIROLOGIE
  • 4. Influenza virus Type A  Influenza A viruses are further classified into subtypes based on the antigenicity of their surface glycoproteins (HA & NA ) Hemagglutinin (HA) Neuraminidase (NA) H1, H2, H3, H4, H5, H6, H7, H8, N1, N2, N3, N4, N5, N6, N7, N8, H9, H10, H11, H12, H13, H14, N9 H15, H16 So far at least 84 serotypes (HA &NA combination) are found in resivour  Infect multiple species Humans Birds (wild birds, domestic poultry) Other animals: pigs, horses, dogs, marine mammals (seals, whales) INSTITUT FÜR VIROLOGIE
  • 5. H5 H5, H7, H9 H3, H7 HA 1-16 NA 1-9 H4, H7, H13 H1 - H3 H1 - H3 H3, H7 H5, H7, H9 H5 INSTITUT FÜR VIROLOGIE
  • 6. How they transmitted ?????????????? The virus is contracted through  Contact with saliva, nasal secretions and feces of the wild birds.  Contaminated surfaces or materials.  Contaminated water * Direct or indirect contact INSTITUT FÜR VIROLOGIE
  • 7. True influenza influenza virus A or influenza virus B Febrile respiratory disease with systemic symptoms caused by a variety of other organisms often called „flu‟ INSTITUT FÜR VIROLOGIE
  • 8. Influenza descriptions Influenza name Strain Host affected Outbreak year Seasonal Flu H3, H1 humans yearly Spanish Flu H1N1 humans 1918 Asian Flu H2N2 humans 1957 Hong Kong Flu H3N2 humans 1968, 1970-72 bird flu H5N1 Poultry, 1997, (endemic in 2003……….. avian), human, & cat Swine flu H1N1 Humans, swine 2009 * H1N2 is currently endemic in humans and pigs INSTITUT FÜR VIROLOGIE
  • 9. Bird Flu: H5N1, H7N7,H9N2… INSTITUT FÜR VIROLOGIE
  • 10. HPAI LPAI H5, H7 H9, H7 H5N1 H9N2 Highly pathogenic viruses result in high Low pathogenicity viruses also cause death rates (up to 100% mortality within outbreaks in poultry but are not 48 hours) in some poultry species generally associated with severe clinical disease INSTITUT FÜR VIROLOGIE
  • 11. transmitted to poultry LPAI virus circulates in Natural reservoir of poultry with mild disease LPAI (H9, H5, H7) virus LPAI Virus Mutates to HPAI with severe disease INSTITUT FÜR VIROLOGIE
  • 13. • The current outbreaks of highly pathogenic avian influenza, which began in South-East Asia in mid-2003, are the largest and most severe on record • Never before in the history of this disease have so many countries been simultaneously affected, resulting in the loss of so many birds INSTITUT FÜR VIROLOGIE
  • 14. Outbreaks map of HPAI H5N1 in poultry (2003 – March 2012) ≥ 100 outbreaks ≥ 10 outbreaks ≥ 1 outbreaks INSTITUT FÜR VIROLOGIE
  • 15. Bird flu: Why is there a risk for humans? Role of pigs as an intermediate host INSTITUT FÜR VIROLOGIE
  • 16. Differences between Pandemics and Epidemics  Pandemics are different from seasonal outbreaks or “epidemics” of influenza  Seasonal outbreaks are caused by subtypes of influenza viruses that are already in existence among people  Pandemic outbreaks are caused by new subtypes or by subtypes that have never circulated among people or that have not circulated among people for a long time INSTITUT FÜR VIROLOGIE
  • 17. Seasonal Epidemics vs. Pandemics Seasonal Influenza Influenza Pandemics – A public health problem – Appear in the human each year population rarely and unpredictably – Usually some immunity built up from previous – Human population lacks exposures to the same any immunity subtype – Infants and elderly most – All age groups, including at risk healthy young adults INSTITUT FÜR VIROLOGIE
  • 18. If a new subtype of influenza A virus is introduced into the human population, most people have little or no protection against the new virus, and if the virus can spread easily from person to person, a PANDEMIC (worldwide spread) may occur INSTITUT FÜR VIROLOGIE
  • 19. Prerequisites for pandemic influenza A new influenza virus emerges to which the general population has little/no immunity The new virus must be able to replicate in humans and cause disease The new virus must be efficiently transmitted from one human to another Ingredients for a pandemic are abundantly available INSTITUT FÜR VIROLOGIE
  • 20. Influenza A viruses are renowned for their rapid evolution in aberrant hosts including humans Antigenic drift occurs when single Antigenic shift takes place when two nucleotides are replaced over time different viruses infect the same cell and through mutations new viral particles are created with new combinations or assortments of the 8 influenza molecules INSTITUT FÜR VIROLOGIE
  • 22. Antigenic shift Sick Pig with both Strands of Influenza INSTITUT FÜR VIROLOGIE
  • 23. 1st pandemics of 21th century Pandemic Year Influenza virus People infected Estimated deaths type worldwide Swine flu 2009– Pandemic > 622,482 (lab- 14,286 (lab-confirmed; 2010 H1N1 confirmed) ECDC 18,036 (lab- confirmed;WHO) The pandemic that began in March 2009 was caused by an H1N1 influenza A virus that represents a quadruple reassortment of two swine strains, one human strain, and one avian strain of influenza; the largest proportion of genes came from swine influenza viruses. INSTITUT FÜR VIROLOGIE
  • 24. History of Reassortment Events in the Evolution of Influenza A H1N1/09 H1N1/ 09 INSTITUT FÜR VIROLOGIE
  • 26. 20th century flu pandemics Spanish flu Asian flu Hong Kong Flu Emergency military hospital Children's ward during Hong Kong Flu Pandemic during Spanish flu pandemic Asian flu pandemic (1968,1970-1972) (1918) (1957) A(H1N1) A(H2N2) A(H3N2) 20-40 m deaths 1-4 m deaths 1-4 m deaths INSTITUT FÜR VIROLOGIE
  • 28. Now literature says… Bird flu can transmitted directly from birds to humans INSTITUT FÜR VIROLOGIE
  • 29. Possible mechanisms for the generation of pandemic influenza viruses INSTITUT FÜR VIROLOGIE
  • 34. http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/gr aph_avian_influenza/graphs_HPAI_31_03_2012.pdf INSTITUT FÜR VIROLOGIE
  • 37. Next warning ? INSTITUT FÜR VIROLOGIE
  • 39. For your kind attention!!!! INSTITUT FÜR VIROLOGIE