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Avian flu (H5N1) Albert Soler Gironès


ORTHOMYXOVIRIDAE

- Subphylum ssRNA (negative polarity)

- RNApolRNAdep-very different from other RNA viruses - Order proposed Multinegavirales: multi-polarity genome (-)

- Features: - Particle pleomorfs - Wrap external cellular lipid - Matrix protein (M1): structural support viral particles


ORTHOMYXOVIRIDAE • In the family Orthomyxoviridae are four different classes:

- Influenza A virus (clinically relevant and are the only ones that have caused pandemics). - Influenza B virus

- Influenza C virus - Thogotovirus


General (Influenza A virus) - 8 RNA genome segments (vRNPs) - Each segment associated with a viral polymerase. - Consisting of three polymerase subunits (PB1, PA and Pb2) and all protected by nucleoproteins (NP).

- Two glycoproteins: hemaglutinin (H1-H16) and neuraminidase (N1-N9). Very important antigenic determinants, jump host pathogenicity,... - Protein m2: ion channel involved in exporting vRNPs the host nucleus. - Other important proteins not present in the virion that are expressed (NS1, PB1-F2).


Viral cycle

Receptor recognition: Hemagglutinin.

Entry of the virion to the cell: from vesicle endocytosis.

Mechanisms of replication: in the nucleus. Independence segments.

Assembly and release: HA activation by proteolysis.


Host-virus Reservoir present in nature

birds

Can affect several guests: pigs, horses, birds, humans and dogs. Skip to host antigenic change (HA and / or NA)

Specificity of receptor that binds host depends on the viral hemaglutinin Link H5N1 preferentially recognizes 2-3, has less affinity for humans. - Sialic acid binding digestive 2-3 birds (avian virus) - Sialic acid binding 2-6 human respiratory virus (human)


Previous flu pandemics in the human • Serological studies in the old people.

• The last three pandemics have been recorded:

- 1918 Spanish flu - 1957 Asian Flu - 1968 Hong Kong Flu


History of influenza pandemics in humans • Spanish flu (1918-1920)

- Subtype H1N1 - Great virulence: Historical context and efficacy virus PB1-F2)

(HA, NA, NS1 and

- 20-40 million deaths (infants, old people and soldiers) - Virus jumps from birds to humans directly - Reappears in 1977 by a leak in a Russian laboratory but does not cause pandemia.

- Could not rebuild in vitro


History of influenza pandemics in humans • Asian flu (1957) - Subtype H2N2 - 1 million deaths - Human virus (H1N1) acquires genes (HA, NA PB1) avian virus

• Hong Kong Flu (1968)

- Subtype H3N2 - 1 million deaths - Human virus (H2N2) avian virus acquires genes - 1889 pandemic subtype H3 immune Notice that leaves decreases mortality rate in older people.


Current: • H5N1 (Avian flu): – Hong Kong in 1997 identified a virus subtype H5N1 (8 deaths of 18 infections). – High virulence in chickens (determined by the genes encoding HA, NA NS1, and PB1-F2) – Reappears in Asian countries in 2003 and 2004 (small differences caused by antigenic drift) – Over 100 cases of people registered since 1997 – Although unable to spread efficiently among humans.


2003

Country cases

2004 deaths

cases

2005 deaths

cases

2006 deaths

cases

2007 deaths

cases

Total deaths

cases

deaths

Azerbaij an

0

0

0

0

0

0

8

5

0

0

8

5

Cambodi a

0

0

0

0

4

4

2

2

1

1

7

7

China

1

1

0

0

8

5

13

8

2

1

24

15

Djibouti

0

0

0

0

0

0

1

0

0

0

1

0

Egypt

0

0

0

0

0

0

18

10

16

4

34

14

Indonesi a

0

0

0

0

20

13

55

45

21

18

96

76

Iraq

0

0

0

0

0

0

3

2

0

0

3

2

Lao People's Democra tic Republic

0

0

0

0

0

0

0

0

2

2

2

2

Nigeria

0

0

0

0

0

0

0

0

1

1

1

1

Thailand

0

0

17

12

5

2

3

3

0

0

25

17

Turkey

0

0

0

0

0

0

12

4

0

0

12

4

Viet Nam

3

3

29

20

61

19

0

0

0

0

93

42

Total

4

4

46

32

98

43

115

79

43

27

306

185


Prophylaxis (Care): • Currently two types vaccine: inactive and grayed - Inactivated influenza virus: purified virus antigens or broken, inactivated virus in two cases (formalin-propiolactona beta)

- Efficiency vaccine depends on two factors: - The age of individuals vaccinated - Similarity antigen vaccine

- Antgripals attenuated: attenuated virus (USA) combination of three attenuated virus is not inactivated administered to healthy people


Pandemic risk in humans: •

Adaptation in human viruses for which a non-immune individuals.

•

Different ways of pandemic occur: - Avian virus jumps to humans directly - Mixing reservoir (permissive species: pigs and pheasants)


Pandemic risk: • Overcome 3 barriers: - Infection - Replication - Spread between humans

• No known factors needed to produce a new virus that is impossible prevention. • In case of pandemic is not as virulent as the last • Important role waterfowl (migratory routes)

• Effect of climate change: new pathogens exposure. • Surely there will be a flu pandemic, if it is not H5N1


Prophylaxis in prespective: • Great progress with the reconstruction in vitro virus 1918 (Interesting to compare non-fatal wave of the deadly virus in 1918)

Problem: First appearance of pandemic viruses causing, after creating vaccines.


Biography •

INFLUENZA: LESSONS FROM PAST PANDEMICS, WARNINGS FROM CURRENT INCIDENTS Taisuke Horimoto*§ and Yoshihiro Kawaoka*‡§ Nature Reviews

Influeza A virus recicling revisited , W.R. DoWdle, Bulletin of World Health Organization

NATURE|Vol 440|27 April 2006, MOLECULAR VIROLOGY Was the 1918 pandemic caused by a bird flu? Arising from: J. K. Taubenberger et al. Nature 437, 889–893 (2005)

Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus Jeffery K. Taubenberger et al.

Clinical Microbiology Reviews, April 2007, p. 243-267, Vol. 20, No. 2 Avian Influenza Virus (H5N1): a Threat to Human Health ; J. S. Malik Peiris,1,2* Menno D. de Jong,3 and Yi Guan1

Science 12 August 2005: Vol. 309. no. 5737, p. 989; Heading Off an Influenza Pandemic ; Edward C. Holmes, Jeffery K. Taubenberger, Bryan T. Grenfell*


Avian Flu