1. Influenza Viruses
Ankit Chauhan
http://ankitvkc.wordpress.com

2. Taxonomical Position

3. • Orthomyxoviridae
member
• Belongs to V Baltimore
System Group
• Family consists of 5
genera:
Influenza - Influenzavirus A
- Influenzavirus B
- Influenzavirus C
- Subtypes(N1,N2,
etc)

4. Structure

5.  A lipid bilayer coat.
 Consists of lipids,
Carbohydrates &
proteins.
Enveloped  Part of host cell
membrane.
 Picked up while leaving
host cell.

6.  Inside protein coat
called CAPSID.
 Helical capsid
symmetry.
Genome  Single stranded RNA.
 Negative sense.
 10-15 kbp.
 Linear
 Composed of 8
segments.

7. Being negative stranded…
• Genetic material is complementary
to mRNA.
• Virus has to convert it into mRNA.

8. Genome encodes 11 proteins…

9.  Hemagglutinin (HA)
 Neuraminidase (NA)
 Nucleoprotein (NP)
 M1 or Matrix protein
Proteins  M2, ion channel protein
 NS1
 NS2(NEP)
 PA
 PB1
 PB1-F2 and
 PB2

11. Electron micrograph
Negatively stained H1N1
x300,000
Courtesy: CDC e-Health

13. Hemagglutinin

14.  Globular head,
projected 10nm
away from viral
HA membrane by a
long stalk.
 Trimer of disulfide-
linked HA1 & HA2
molecules.

15. Functions…
 Mediate viral fusion with cellular membranes during
entry.
 Docking Protein.
 Essential for virus assembly.
 Membrane-distal globular domain possess:-
-Binding site for the sialic acid
virus receptors.
-Sites of Antigenic variation.
Hemagglutinin is a spike-shaped virus
surface protein

16. HA in action

17. “HA binds to the Sialic Acid
Receptors on the
host cell”

18.  Surface
glycoprotein.
 Characterized by
Sialic Acid Receptors galactose alpha-2,6
& alpha-2,3 linkages
to a molecule of N-
acetyl muramic acid.

20. “The HA proteins of Influenza A
Viruses are primed for the
dramatic conformational changes
to allow the entry of internal virion
components into a host cell.”

21. Types of Hemagglutinin
Type 1 HA Type 2 HA
Specifically target Humans Infects Birds
Binds to alpha-2,6 linked Binds to alpha-2,3 linked
sialic acid receptors sialic acid receptor
Exception:- Pigs. They have both Human & Avian sialic
acid residue receptors. Allowing them to be infected
by both types simultaneously.

22. Neuraminidase

23.  Surface Protein
 Releases virus from the
Host cell.
 Cleaves
terminal sialic acid
residues
from glycan structures
on the surface of the
infected cell.
Crystallographic structure of
influenza A N9 neuraminidase

24. M1

25.  A matrix protein.
 Forms a coat inside
the viral envelope.
M1  Binds to the
viral RNA.
 Has multiple
regulatory
functions.

26. M2 Pore

27.  A proton-selective ion
channel protein.
 A homo-tetramer.
M2  Located in the viral
envelope
 Activated by low pH.

28. “It enables hydrogen ions to enter the
viral particle (virion) from
the endosome, thus lowering pH of the
inside of the virus, which causes
dissociation of the viral matrix protein
M1 from the ribonucleoprotein RNP.
This is a crucial step in uncoating of the
virus and exposing its content to
the cytoplasm of the host cell. .”

29. Replication

30. Host cell invasion and replication
by the influenza virus:-

31. Transmission

32. Aerosolization

34. Aerosolization
Contaminated surfaces

37. Symptoms

38.  Body aches
 Extreme coldness
and fever.
 Body aches, especially
joints and throat
 Extreme coldness and fever
 Fatigue
 Headache
 Irritated watering eyes
 Reddened eyes, skin,
mouth, throat and nose
 Gastrointestinal symptoms
such
as diarrhea and abdominal
pain

40. Tropism

41. “The specificity of a virus for a
particular host tissue, determined in
part by the interaction of viral
surface structures with receptors
present on the surface of the host
cell.’’

42. Receptor specificity determines cell tropism of influenza
viruses in differentiated cultures of human airway
epithelium. Human virus preferentially infects non-ciliated
cells (left image), whereas avian virus mainly infects ciliated
cells (right image). The cultures were double-
immunostained for virus antigen (red) and for cilia of ciliated
cells (black).

43. Epidemics

44.  Peak prevalence in
winter.
 Two different flu
seasons each year.
 3-5 m cases of severe
Flu illness.
 Up to 500,000 deaths
worldwide/year.
 More than 200,000
hospitalizations/year.

45. Pandemics

46. Name of Date Deaths Subtype Pandemic
pandemic involved Severity
Index
Asiatic 1889–1890 1 million H2N2 NA
(Russian) Flu Possibly
1918 flu 1918–1920 20 to 100 H1N1 5
pandemic million
(Spanish flu)
Asian Flu 1957–1958 1 to 1.5 H2N2 2
million
Hong Kong 1968–1969 0.75 to 1 H3N2 2
Flu million
2009 flu 2009–Present H1N1 H1N1 Above 5
pandemic

48. “Flu virus-a slippery customer”.

49. • The main types of influenza viruses in humans. Solid
squares show the appearance of a new strain,
causing recurring influenza pandemics. Broken lines
indicate uncertain strain identifications

50. Influenza A HA and NA Subtypes
H1 N1
H2 N2
H3 Other Animals
N3
H4 Other Animals N4
H5 Other Animals N5
H6 N6
H7 Other Animals
N7 Other Animals
H8 N8 Other Animals
H9 N9
H10
H11
H12
H13
H14
H15
50
H16

51. Mutation

52. Antigenic drift
2 types
Antigenic shift

53.  Random mutations in the
genes
 Changes the antigens of
Drift the virus.
 Virus evade the immune
system.
 Associated with Epidemic.

54.  2 different strains
combine to form a new
subtype.
Shift  New subtype has
mixture of the
surface antigens of the
two original strains.

58. Distinguishing symptoms

59. How to conceptualize the god
damn reassortment?

61. Numbers…

65. Prevention & Control

66. Vaccination
 Developing
Prevention vaccine depending
upon the
circulating strain.

67. Administration of a vaccine
during the 1976 New Jersey
immunization project, for
Influenza A (swine flu).
Use of a jet injector during
the 1976 New Jersey
Influenza A immunization
project. 45 million adults in
the United States received a
vaccine containing the
A/New Jersey/76
influenzavirus ("swine flu"
virus).
Courtesy:- CDC e-health

69. Control

70. Hand washing

71. Avoiding
spitting

72. Covering the nose and
mouth when sneezing
or coughing

73. Use alcohol-based
hand rubs/antiseptic
solutions.

74. Use of masks in public
places.

75. Treatment

76. M2 Amanatadine
inhibitors Rimantadine

77. • The antiviral
drugs block a
viral ion
channel (M2
protein) and
prevent the virus
from infecting
cells.

80. Oseltamivir (trade
Neuraminidase name Tamiflu
inhibitors Zanamivir (trade
name Relenza)

81. “Neuraminidase
inhibitors are
designed to halt the
spread of the virus
in the body by
blocking the active
site of
neuraminidase.”

84. Relative Costs of 5-Day Treatment Courses
Amantadine: $3.70
Rimantadine: $20.40
Oseltamivir: $63.40
Zanamivir: $51.40

85. Most of All,

86. “Avoid adopting any
misconceptions and stay
informed about the Do’s and
Don’ts while the prevalence of
any kind of flu.”

87. References
• Lecture on Virology (Spring 2008) by Derek Wood,
Astt. Prof. of Biology, Seattle Pacific University, U.S.
(Podcast available on iTunes Store).
• The Structure of H5N1 Influenza Virus
Glycoproteins, lecture by Sir John Skehel, National
Institute for Medical Research (NIMR), U.K. Dated
13th Dec;2006. (Podcast available on iTunes Store).
• Principles of Virology by S.J. Flint et. Al.

89. Thanks