This document provides an overview of influenza viruses including what influenza is, the history and classification of influenza viruses, their structure and types (A, B, C), how they change through antigenic drift and shift, examples of avian and swine influenza, seasonal flu vs pandemics, and treatment for H1N1 flu. It discusses that influenza A viruses can infect humans and animals, cause pandemics, and are the subject of antigenic drift and shift. Influenza B primarily infects humans. It also summarizes that the 1918, 1957, and 1968 pandemics were caused by antigenic shifts in influenza A viruses H1N1, H2N2, and H3N2 respectively.

1. Influenza
A/H1N1
RASHA mohamed mahmoud
virology

2. Contants
• What is Influenza ?
• History of influenza
• Influenza Classification
• Structure of influenza
• Types of influenza viruses
• How Influenza Viruses Change
• Avian influenza
• Swine influenza- Influenza A 2009 H1N1
A / Mexico / 001 / 2009 (H1N1)
• Seasonal flu/ Pandemic
• Treatment for H1N1 flu

3. What is Influenza ?
 Influenza, commonly known as "the flu",
is an infectious disease of birds and
mammals caused
 Influenza (the flu) is a contagious
respiratory illness caused by influenza
viruses. It can cause mild to severe illness,
and at times can lead to death.
Resistance of Virus
 Inactivated by heating at 500c
for 30 mt
 Survive for 1 week at 0 – 40c for 1
week
 Ether, formaldehyde, Phenol
destroy the virus

4. Early Recognized Pandemics
•The first recognized pandemic occurred
in July and August of 1510 when an
outbreak of “gasping oppression”
appeared nearly everywhere at once. It
was described as a “„gasping
oppression‟ with cough, fever, and a
sensation of constriction of the heart and
lungs”, leaving an impression strong
enough for people to write of it decades
later (Morens et al, 2010). At least seven
contemporary and near-contemporary
reports exist of the 1510 pandemic
(Morens, North & Taubenberger, 2010).
History of influenza

5. Dr.T.V.Rao MD 5
Circulating Influenza Strains and
Pandemics in The 20th Century
1920 1940 1960 1980 2000
H1N1
H2N2
H3N2
1918: “Spanish Flu” 1957: “Asian Flu” 1968: “Hong Kong Flu”
20-40 million deaths 1-4 million deaths 1-4 million deaths

6. History of influenza
• H1N1, which caused Spanish flu in
1918, and the 2009 flu pandemic
• H2N2, which caused Asian Flu in
1957
• H3N2, which caused Hong Kong Flu
in 1968
• H5N1, a current pandemic threat
• H7N7, which has unusual zoonotic
potential
• H1N2, endemic in humans and pigs
• H9N2
• H7N2
• H7N3
• H10N7

7. Influenza Classification
the family
Orthomyxoviridae
single-stranded RNA
viruses
3 basic types of virus
A, B, C
structural and
biological similarities
but vary antigenically

8. Types of influenza viruses
Influenza viruses divided into 3main types: influenza A, B, and CA
viruses
 Infect birds and other animals, as well as humans
Source of seasonal influenza epidemics and all
pandemics
Causes an average 30,000 deaths per year
 Especially dangerous for the elderly
B and C viruses
infect humans only and do not cause pandemics
virus C infections - much milder

9. Influenza A virus
Influenza A virus: the most virulent human pathogens among
the three influenza types.
Influenza A virus : capable of infecting human as well as
animals (ducks, chickens, pigs, whales, horses and seals). Wild
aquatic birds are the natural hosts for a large variety of influenza
A.
Influenza A virus is the main cause of worldwide pandemics.
Influenza A viruses subtypes e.g., (H1N1), (H5N1)

10. Influenza B virus
Influenza B virus|: it almost exclusively infects
humans.
Influenza B virus: less common than influenza A.
Influenza B viruses are not divided into subtypes,
but can be further broken down into different strains.
Influenza B virus: mutates at a rate 2–3 times lower
than type A. This reduced rate of antigenic change,
combined with its limited host range ensures that
pandemics of influenza B do not occur

11. Influenza C virus
Influenza C virus: infects humans.
Influenza C virus; less common than the other types
and usually only causes mild disease in children.

12. Viral structure
Virus are spherical in shape
Size is 80 -120 nm
Pleomorphism is common with variant
forms
A negative sense Single stranded RNA
genome is segmented into 8 segments
The nucelocapsid is surrounded by an
envelope with inner membrane protein
layer and outer lipid
From the envelop there are projections
of two types
- Hem agglutinins
- Neuraminidase

13. The Influenza A Capsid
 The influenza A capsid contains the antigenic Glycoproteins
Hemagglutinin (HA) and neuraminidase (NA): Several hundred molecules
of each protein are needed to form the Capsid . 12. The Influenza A
Genome
The influenza A genome
 Encoding for 11 proteins: Hemagglutinin (HA), Neuraminidase (NA),
nucleoprotein (NP), M1, M2, NS 1, NS2 (NEP/nuclear export protein), PA,
PB1 (polymerase basic 1), PB1-F2 and PB2.

14. N
H

15. How Influenza Viruses Change
There are two ways that influenza virus changes –
these are called Drift and Shift.
Antigenic Shift
It is abrupt and Drastic change
•Major change, new subtype
•Caused by exchange of gene segments
•May result in pandemic
Example of antigenic shift
•H2N2 virus circulated in 1957-1967
•H3N2 virus appeared in 1968 and completely replaced H2N2 virus

16. Antigenic Drift
Is a gradual, continuous
change
•Minor change, same subtype
•Caused by point mutations in gene
•May result in epidemic
Example of antigenic drift
•In 2002-2003, A/Panama/2007/99 (H3N2) virus
was dominant
•A/Fujian/411/2002 (H3N2) appeared in late 2003
and caused widespread illness in 2003-2004

18. Avian influenza
 Avian influenza is an infectious disease of birds
caused by type A strains of the influenza virus.
 These viruses occur naturally among wild aquatic
birds worldwide and can infect domestic poultry and
other bird and animal species. The disease, which was
first identified in Italy more than 100 years ago
 The first case of a bird flu virus infecting a person
directly, H5N1, was in Hong Kong in 1997. Since
then, the bird flu virus has spread to birds in countries
in Asia, Africa and Europe
•Influenza A virus
•subtype H5N1

19. Avian influenza
 The influenza virus must attach to specific proteins ( receptors) . It is the hem
agglutinin, or HA, which infect cells high in the respiratory tract, the H5N1 HA protein
attaches to cells much lower in the respiratory track. The virus is so deep within the
respiratory tract . If the HA protein of H5N1 were to mutate so that it could infect cells
higher in the respiratory tract, then it would more likely be able to pass from person to
person
 H5N1. These include the H7N2 strain which infected two in United States in 2002 ,
2003, and the H9N2 strain in Asia in 1999 and 2003. The H5N1 virus was of greatest
concern because of its rapid mutation rate,
 Spring of 2013, new subtype infect humans. This variant influenza A (H7N9) in last
detected in birds, but never in humans. May 2013, 132 cases and 37 deaths were
reported to the WHO; all cases occurred in China. The virus does not appear to spread
easily from person to person, but influenza viruses are highly mutable and it is possible
that H7N9 could spread more readily over time

21. Swine influenza
Swine influenza (also called H1N1 flu, swine flu, hog flu, and
pig flu) is an infection by any one of several types of swine
influenza virus. Swine influenza virus (SIV) is any strain of the
influenza family of viruses that is endemic in pigs
This can lead to a dangerous mixing or reassortment of different
influenza types, resulting in the creation of new virus subtypes.

22.  The H1N1 subtype of influenza A virus has caused substantial morbidity
and mortality in humans, first documented in the
 global pandemic of 1918 and continuing to the present day. Despite this
disease burden, the evolutionary history of the
 A/H1N1 virus is not well understood, particularly whether there is a
virological basis for several notable epidemics of
 unusual severity in the 1940s and 1950s. Using a data set of 71
representative complete genome sequences sampled
 between 1918 and 2006, we show that segmental reassortment has played
an important role in the genomic evolution of
 A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate
from the 1947 epidemic acquired novel PB2 and HA
 genes through intra-subtype reassortment, which may explain the abrupt
antigenic evolution of this virus. Similarly, the
 1951 influenza epidemic may also have been associated with reassortant
A/H1N1 viruses. Intra-subtype reassortment
 therefore appears to be a more important process in the evolution and
epidemiology of H1N1 influenza A
Swine influenza

23. Schematic representation of the phylogenetic patterns of all eight
A/H1N1 influenza virus genomes used in this study

24. A new “swine” flu emerges
 The new H1N1 virus appears to be made up of a novel
combination of segments from four different influenza
virus strains - a Eurasian swine virus, a North
American swine virus, and avian and human influenza
virus segments (probably as a result of the mixing of a
swine/avian/human triple assortment virus with the
Eurasian swine virus, with H1 derived from a classical
swine virus and N1 from the Eurasian virus).

25. Viral Re-assortment
Reassortment in pigs
Reassortment in
humans
Pandemic Influenza
VirusDr.T.V.Rao MD 25

27.  the 1918-1919 Spanish pandemic (influenza virus
 subtype H1N1)
 the 1957 pandemic (subtype H2N2)
 the 1968-1969 pandemic (Hong Kong subtype H3N2)
 and, to a lesser extent, the Russian pandemic in 1977 (subtype H1N1)
FluEpidemic (seasonal) influenza
which occurs annually and is attributable to minor changes in genes that
encode proteins on the surface of circulating influenza viruses. These are
known as interpandemic epidemics.
Pandemic influenza
 which occurs when more significant changes in the influenza A virus
arises when human virus strains acquire genes from influenza viruses of
other animal species. When this happens, everyone in the world is
susceptible to the new virus, and a worldwide epidemic or pandemic can
result.
Seasonal flu/ Pandemic

28. Treatment for H1N1 flu
Chemotherapy
 The 2009 H1N1 flu was sensitive to two antiviral drugs used
to treat influenza - Tamiflu® (oseltamivir) and Relenza®
(zanamivir).
 The drugs act by inhibiting the essential neuraminidase
protein (the “N” protein in the naming system). Proper use of
these drugs can shorten the duration and lessen the severity of
the sickness and reduce the chance of spreading the disease.
 Tamiflu can therefore be used to reduce the length of illness
and its transmission within a household.
 Resistance of H1N1 strain to oseltamivir has been reported at
25% ,

29. Influenza is a Global Concern Be
Familiar with Facts

30. Major References
•WHO current issues on Influenza
•CDC Literature on facts, and prevention
 Palese P (January 2006). "Making better influenza virus vaccines?". Emerging Infect. Dis. 12 (1):
61–5. doi:10.3201/eid1201.051043. PMID 16494719.
 WHO (PDF) contains latest Evolutionary "Tree of Life" for H5N1 article Antigenic and genetic
characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as
pre-pandemic vaccines published 18 August 2006
 WHO's assessment of Flu Research as of November 2006.
http://www.cdc.gov/flu/about/disease/
http://www.wepapers.com/Papers/69348/Swine_Flu_The_virus_and_the_ma
ss_vaccination_campaign.ppt. Clancy, S. (2008).
Genetics of the influenza virus. Nature Education 1. Available from:
http://www.nature.com/scitable/topicpage/genetics-of-the- influenza-virus-716 J Infect Dis. Swine
influenza virus infections in humans. 1977 Dec;136 Suppl:S386-