THE EMERGENCE OF NOVEL

INFLUENZA STRAINS

Lourens Robberts, PhD, D(ABMM), FCCM

Clinical Microbiologist

Director

2012

Influenza virus• Types A, B and C

• segmented genome

• ss RNA (single stranded, negative sense)Haemagglutinin

Neuraminidase

Influenza A virus ecology

Intra-species transmission Inter-species transmission

Influenza: what does it do?

Influenza in Chicken H5N1 - Kam Tin, 2002Courtesy of Dr H Wong & L Sims, AFCD

Transmission of influenza viruses

• Transmitted by droplets through the coughing and sneezing of infected persons

• Transmitted by

fomites

Human influenza: The illness

Normal cells Infected cells

Human influenza: Epidemics

Protection from influenza

• Immune response (antibody to the virus haemagglutininand neuraminidase) protects from re-infection

• RNA viruses mutate rapidly

• Change in H and N

• Escape from prior immunity

• Antigenic “drift”

Influenza Pandemics in History

• In 1957 ‘Asian’ influenza caused more

than 1 million deaths

• In 1968 ‘Hong Kong’ influenza caused

more than 1 million deaths

• In 1918 ‘Spanish’

influenza caused

40 million deaths

2

Human influenza pandemics

How do the H and / or N glycoproteins change completely ?

Generating a pandemic virus

• mixing of the genes of two viruses - human and animal

• Genetic reassortment

The origin of pandemic influenza viruses

Pandemic influenza• Derived in part or whole

from avian influenza viruses

• Aquatic birds and domestic ducks - the reservoir of influenza viruses

• Subtypes: Haemagglutinins 1-16 Neuraminidase 1-9

Sialic acid distributes preferentially to the apical domain of cultured epithelial cells

expressing sialic acid predominantly in either α2, 3 or α2, 6 linkage.

Ulloa F , Real F X J Histochem Cytochem 2001;49:501-509

Avian-humanspecies barrier

N-acetylneuraminic acid-α2,3-galactose linkage on sialyloligosaccharides

α2-3 α2-6

Ito, T. JV 1998

• Pigs are susceptible to both human and avian influenza viruses. • A “mixing vessel” for the genesis of pandemic influenza.

Where can avian and human viruses meet,to exchange their genes ?

How do animal influenza viruses adapt to efficient human – human transmission ?

Pigs: A “mixing vessel”

Reassortment in humans“human mixing vessel”

Reassortment of avian and human influenza virus genes

The H5N1 incident in 1997

Epidemic Curve of Influenza A (H5N1)

Cases in HKSAR, May - Dec 1997

0

1

2

3

4

5

6

7

15-M

ay

06-J

un

11-J

un

06-J

ul

10-J

ul

03-A

ug

17-A

ug

31-A

ug

12-S

ep

16-S

ep

12-O

ct

26-O

ct

01-N

ov

09-N

ov

16-N

ov

23-N

ov

30-N

ov

07-D

ec

12-D

ec

21-D

ec

26-D

ec

29 D

ec

Dates of onset (Beginning of week)

No

. o

f C

ases

Recovered Deceased

The H5N1 incident in 1997

• ~ 20% of chicken in live poultry markets carry H5N1 virus• patients with H5N1 disease had contact with live poultry markets

December 1997• Decision to slaughter all poultry in farms and markets in Hong Kong

• No further human H5N1 cases after the poultry slaughter

Epidemic Curve of Influenza A (H5N1)

Cases in HKSAR, May - Dec 1997

0

1

2

3

4

5

6

7

15-M

ay

06-J

un

11-J

un

06-J

ul

10-J

ul

03-A

ug

17-A

ug

31-A

ug

12-S

ep

16-S

ep

12-O

ct

26-O

ct

01-N

ov

09-N

ov

16-N

ov

23-N

ov

30-N

ov

07-D

ec

12-D

ec

21-D

ec

26-D

ec

29 D

ec

Dates of onset (Beginning of week)

No

. o

f C

ases

Recovered Deceased

The H5N1 incident in 1997

• What is the source of the human infection?

• How did the virus arise ?

Humans and Chicken

H5N1 Gs/GD/96-like

H5N1/97

H9N2 G1-like H6N1 W312-like

PB2

PB1PAHA

NP

NA

M

NS

PB2

PB1PA

HA

NP

NA

M

NS

PB2

PB1PA

HA

NP

NA

M

NS

PB2

PB1

PA

HA

NP

NA

M

NS

1997

Guan et al 1999PNAS

Not detectedafter 1997

The origin of the 1997 H5N1 virus

H9N2H6N1

H5N1 (Gs/Gd)

H5N1

H9N2H6N1

H5N1/97 -like

Amplifier

Mixing vessel

Evolution of H5N1

viruses: 1996-2004

Guan et al PNAS 2002Guan et al PNAS 2004Li et al Nature July 8, 2004

Evolution of H5N1

viruses: 1996-2004

Guan et al PNAS 2002Guan et al PNAS 2004Li et al Nature July 8, 2004

NS1

M2

Evolution of H5N1

viruses: 1996-2004

Guan et al PNAS 2002Guan et al PNAS 2004Li et al Nature July 8, 2004

Japan

SE Asia

2009: pH1N1 (Swine)

Han et al. J Pub Health Epidemiol 2011

A/California/7/2009 (A/H1N1 component, A H1N1 pdm09) 8/8 *A/Perth/16/2009 (A/H3N2 component) 27/27 *

B/Brisbane/60/2008 (Victoria lineage) 14/26 *

B/Wisconsin/01/2010-like (Yamagata lineage) 12/26

Examples of vaccine components