non

1. Orthomyxoviridae
• Is enveloped virus, helical nucleocapsid
• and segmented (-RNA) genome comprises the
influenza virus.
• Key viral proteins:
• 1) Envelop glycoprotein: are the major
antigen for influenza virus.
• -a) Haemogglutinin (HA) functions are viral
attachment protein and also binds to an
aggregates erythrocytes (hemagglutination)

2. Key cont…
• b) Neuraminidase (NA): an enzyme that removes
sialic acid from virion and host glycoproteins and
glycolipids facilitates release of virions from target
cells by minimizing clumping.
• 2. Nucleoprotein and RNA dependent RNA
polymerase associated with genomic segment to
form helical nucleocapsids.
• 3. MI ( Matrix protein surrounds the nucleocapsid
and is involved in virion assembly.
• 4. M2 (membrane) protein which forms channel that
facilitates uncoating and assembly, is target for
amantadine and rimantadine antiviral drugs

4. Types and Genetics changes in
influenza viruses
• Three types A, B and C
• Influenza type A&B are significant human pathogens
Influenza while type C is less important. Type A
influenza infect human as well as animals.
• a) antigenic drift: minor changes due to mutation in
the genes encoding HA or NA , which alters viral
antigenicity. Both Influenza A and B exhibit antigenic
shift.
• b) Antigenic shift: major changes that result
reassortment of genome segments from different
human and / or animal strain.

5. • Only influenza A undergoes antigenic shift
• Randon mixing and packaging of genome
segments into virions occur after co –
infection with different strains of viruses,
producing new hybrid viruses.
• For example: reassortment of swine influenza
virus (genome segment S1-8) and human
influenza virus (segment H1-8) could create a
new, distinct hybrid strain that contain some
swine and some human segments and is
capable of infecting humans.

6. Replication
• Attachment and entry: after HA binds to sialic-
acid containing receptors on epithelial cells,
virions enter by endocytosis.
• Fusion with endosome and un-coating: release of
the nucleocapsid from internalized virion is
facilitated by acidification of the endosome and
M2 proton channel
• Nucleic acid synthesis: following release
nucleocapsid, viral RNA polymerase carried in the
virion moves to the nucleus where it produces
mRNA and progeny genome segment.

7. Replication cont……
• Enveloped: after nucleocapsid assemble, they
move to the plasma membrane, associated
with matrix protein, become surrounded by
virus- modified membrane , and are released
by budding.

8. Laboratory identification
• Elisa
• Hem adsorption
• Hemagglutination

9. Pathogenesis and host response
• Killing of ciliated and mucus secreting epithelial
cells results from initial infection of upper
respiratory tract.
• Action of viral neuramidase (NA) thins (weaken)
out mucous secretion, comprising airway
clearance and promoting viral spread to the
lungs, as well as secondary bacterial infections.
• Virus or bacteria induced tissue damage can
cause pneumonia.

10. • Interferons produced in response to infection
help control viral spread but are largely
responsible for typical “flu like” symptoms.
• Strain – specific antibody response to HA and
NA antigens provides no protection against
subsequent infections by different strains
• Cell mediated response, which recognizes
peptides from less variable proteins (eg
nucleoprotein) provide more general
protection that can help reduce subsequent
disease by different strain.

11. Diseases due to Influenza viruses
• 1. Classic acute influenza in adult:
• a) Time course: incubation period is 1-3 days.
Prodromal period is 3- 24 hours , diseases
usually lasts about 1 week.
• b) Clinical manifestations: malaise and head
ache during prodrome are followed by
myaglia, fever, and non-productive cough.
• Secondary bacteria infection (eg. Sore throat) may
occur in the second week.

12. • C) Severity: diseases may be asymptomatic to
severe depending on the degree of existing
immunity to the infecting strain and other
factors
• Severe illness occurs most often in pregnant
women and in patients with
immunodeficiencies or cardiorespiratory
diseases.

14. Epidemiology
• Influenza epidemics involving all age groups
occur each winter; worldwide pandemics
appear irregularly.
• Changes in the hemagglutinin and
neuraminidase surface antigens are
responsible for the appearance of
antigenically novel strains that evade host
immunity and cause reinfections

15. Childhood influenza
• Post influenza: disease is similar to that in
adult but with higher fever, croup, otitis
media, bronchitis, abdominal pain, and
vomiting are like to be present
• Complications: post-influenza encephalitis
with inflammation may occur 2-3 weeks after
recovery, rarely fatal.
• Myositis and aspirin associated Rey
_Syndrome may occur in children

16. Transmission
• Respiratory droplets: are primary means of
spreading influenza virus.
• a) Local outbreak (epidemics) due to antigenic
drift (change in viral antigenicity ) occurs
every few years.
• B) Widespread outbreak (pandemic) due to
antigenic shift (appearance of new strain)
occur approximately every 10 years

17. Prevention and Treatment,
• 1. Formalin – killed flu vaccine consisting of
the predicted endemic strain is produced each
year year
• Immunization is recommended for at risk
population particularly elderly,
immunodeficient patients and those with
cardiorespiratory diseases.

18. Treatment cont…
• Amantadine and rimantadine: they block
uncoating of endocytosis virions, are approved
for use against influenza A in unimmunized
individuals but are ineffective against
influenza B.
Treatment must start before or within 24
48 hours of appearance of symptoms
Zanamivir and oseltamivir inhibit neuraminidase
and are effective against both influenza A &B.
Acetaminophen(not asprin) can reduce
symptoms of influenza

19. The Influenza A virus subtypes that have been confirmed in
humans, ordered by the number of known human pandemic
deaths, are:
• H1N1 caused "Spanish Flu" and the 2009
swine flu outbreak (novel H1N1)
• H2N2 caused "Asian Flu"
• H3N2 caused "Hong Kong Flu"
• H5N1 is "bird flu", endemic in avians
• H7N7 has unusual zoonotic potential
• H1N2 is currently endemic in humans and pigs
• H9N2, H7N2, H7N3, H10N7