Influenza viruses are enveloped viruses with segmented, single-stranded RNA genomes that cause influenza in humans and some animals. There are four main types of influenza viruses: A, B, C, and D. Types A and B cause seasonal epidemics in humans. Influenza A viruses bind to host cells using hemagglutinin and release from cells using neuraminidase. They replicate in the nucleus and bud from the cell surface. Seasonal epidemics are driven by antigenic drift, while pandemics arise through antigenic shift. Influenza spreads through respiratory droplets and causes fever, cough, and muscle aches. Diagnosis is through viral culture, rapid tests, or PCR. Vaccination and antiv

1. ORTHOMYXOVIRUSES:- INFLUENZA

2. o Family:-orthomyxoviridae
o Genus:-orthomyxovirus
o Shape:-spherical enveloped virus with a lipid bilayer
o Diameter:-80-120nm
o Helical nucleocapsid ,that consists of a nucleoprotein and a
multipartite genome of single stranded –ve sense RNA in 7/8
segments
o Envelope carries a (hemagglutinin(H) attachment protein and a
neuraminidase(N) (glycoprotein spikes)
N/b:envelope is derived from host cell membrane

3. STRUCTURE

4. VIRAL PROTEINS
oHemagglutinin:-binding of virions to host cell via sialic acid receptors,its also
responsible for fusion of virus envelope with endosomal membrane.
oNeuraminidase:-Its an enzyme that destroys cell receptor to which hemagglutinin
attaches this aids in the release of newly formed virions to uninfected host cells.
oM1-protein/Matrix protein:-gives strength and rigidity to lipid envelope
oM2-ion channel:-facilitates release of nucleocapsids from the virion
oPB2,PB1,PA:-RNA polymerase components essential for RNA and viral replication
oNP:-encapsidates virus genome for the purposes of RNA transcription, replication
and packaging.

5. CLASSIFICATION
 Influenza viruses are divided into 4 types (A,B,C and D)
 Type A & B are associated with most clinically important human diseases &
seasonal epidemics, because they undergo genetic variation that forms the
basis of the new strains.
 Type C is antigenically stable(mild cold like symptoms, including fever.dry
cough, headache muscle pain, achiness.
 Type D is a bovine influenza virus that was isolated in 2012.
 There are 18 types of hemaglutinin (HA1-18) and 9 types of
neuraminidase(NA1-11) which give 194 combinations of these proteins

6. CLASSIFICATION
Type A is divided into different serotypes based on antibody response to the
viruses.(H1N1-swine flu 2009,spanish flu 1918),(H2N2-asian flu in
1957),(H3N2-hongkong flu in 1968),(H5N1 bird flu in 2004),(H7N7 has unusual
zoonotic potential)
(H7N9-bird flu in 2013),(H1N2-endemic in humans pigs & birds).
Others include (H9N2,H7N2,H7N3 & H1N7).
Type B mostly infects humans ,its less common than type A,It mutates 2-3 times
slower than A,it lacks antigenic diversity.
Immunity can be acquired at an early age,however type B mutates enough that
lasting immunity is not possible.
Type C Infects humans,dogs & pigs.it sometimes causes mild disease in
children.

7. REPLICATION CYCLE

8. REPLICATION CYCLE
•Virus attaches to sialic acid receptors on the host cell surfaces of epithelial cells, typically in the
nose, throat, and lungs of mammals, and the intestines of birds via hemagglutinin gpt.
•It then undergoes endocytocis following cleavage of hemagglutinin by proteases
•Fusion of virus particle and endosomal membrane then occur as a result of (HA) fusing with
viral envelope
•Uncoating of virus particle follows acidification of core of virus allowing release of viral RNA &
core proteins into cytoplasm.as a result of M2 ion channels, which allow protons through.
•Entry into nucleus:-Viral RNA & core proteins are then transported into the nucleus.RNA
transcriptase, transcribes +ve sense vRNA from –Ve sense vRNA,this vRNA either is transported
to cytoplasm/remains in nucleus where it is translated.
•Newly synthesized viral particles are either secreted through Golgi apparatus to cell surface(HA
& NA)/transported back to nucleus to bind vRNA
•Negative-sense vRNAs that form the genomes of future viruses, RNA-dependent RNA
polymerase, and other viral proteins are assembled into a virion. HA and NA molecules cluster
into a bulge in the cell membrane. The vRNA and viral core proteins leave the nucleus and enter
this membrane protrusion The mature virus buds off from the cell in a sphere of the host
phospholipid membrane, acquiring hemagglutinin and neuraminidase with this membrane coat

9. PATHOGENESIS
Influenza is acquired by inhaling aerosolized respiratory secretions
from a person with the disease.
Following transcription, nucleocapsid assembly & subsequent release
of progeny virus having acquired HA & NA glycoproteins embedded
on host cell membrane, after 6 hrs the virus spreads rapidly to nearby
cells including mucus secreting cells & alveoli cells. Infected cells die
and slough off which destroys mucocilliary escalator and severely
impairing one of the body's major defense against infection. In majority
of cases immune response controls infection however complete
recovery might take 2 months/more. Only a small no die but epidemics
which are widespread cause a high no of deaths. more often death
occurs due to bacterial secondary infections due to Staphylococcus
aureas,streptococcus pyogenes,/haemophillus influenzae.

10. EPIDEMIOLOGY
yearly influenza epidemics can affect all populations, but children younger than the
age of two, adults older than 65, as well as the people with chronic medical
conditions or weakened immune systems bear the highest risk of complications.
Annual attack rate is estimated at 5–10% in adults and 20–30% in children.
In temperate climates seasonal epidemics of the virus occur mainly during the
winter time, compared to tropical regions where it may occur throughout the
year, resulting in much more irregular outbreaks. This is why the World Health
Organization assisted by the National Influenza Centers makes recommendations
for two different vaccine formulations every year; one for the Northern, and one
for the Southern Hemisphere.
The epidemics caused by the influenza virus are estimated to result in about 3 to 5
million cases of severe illness, and up to 500 thousand deaths worldwide.(Nov 9
2014)

11. ANTIGENIC DRIFT
antigenic drift, is a process in which mutations to the virus genome produce
changes in the viral HA or NA. Drift is a continuous ongoing process that results
in the emergence of new strain variants. The amount of change can be subtle
or dramatic, but eventually one of the new variant strains becomes dominant.
drift affects the influenza viruses that are already in worldwide circulation. This
process allows influenza viruses to change and re-infect people repeatedly
through their lifetime and is the reason the influenza virus strains in vaccine
must be updated each year.

12. ANTIGENIC SHIFT
Antigenic shift is a more major change in the influenza virus. This shift occurs typically when
a human flu virus crosses with a flu virus that usually affects animals (such as birds or
pigs).
When the viruses mutate, they shift to create a new subtype that is different from any seen in
humans before.
This can happen in three ways:
• A human flu virus infects an animal such as a pig. The same pig also gets infected by a flu
virus from another animal such as a duck. The two flu viruses can mix and mutate, creating
a completely new type of flu virus which can then spread to humans.
• A strain of bird flu passes to humans without undergoing any type of genetic change.
• A strain of bird flu passes to another type of animal (such as a pig) and is then passed on to
humans without undergoing a genetic change.

13. CLINICAL MANIFESTATIONS
Influenza viruses are spread from person to person primarily through large-particle respiratory
droplet transmission e.g., when an infected person coughs or sneezes near a susceptible
person/Contact with contaminated surfaces /airborne transmission of particles that remain
suspended in air for long periods
 incubation period for influenza is 1—4 days (average: 2 days)
Uncomplicated influenza illness is characterized by symptoms such as (fever, myalgia,
headache, malaise, nonproductive cough, sore throat, and rhinitis). Among children, otitis
media, nausea, and vomiting also are commonly reported with influenza illness.
Uncomplicated influenza illness typically resolves after 3—7 days for the majority of persons.
Complicated influenza is defined as influenza requiring hospital admission and/or with
symptoms and signs of lower respiratory tract infection (hypoxaemia, dyspnoea, lung
infiltrate), central nervous system involvement and/or a significant exacerbation of an
underlying medical condition.Recovery might take 2 months or more

14. DIAGNOSIS
 Virus Isolation Using Cell Culture Approaches
 Immunofluorescence assays
 Serological assays
 Nucleic acid amplification tests
 Rapid diagnostic tests
Virus Isolation Using Cell Culture Approaches
Viral Culture:-involves inoculation of permissive cell lines or
embryonated eggs with infectious samples, propagation for 7–10
days to monitor development of cytopathic effect, and final
confirmation of influenza virus infection by specific antibody
staining, hemadsorption using erythrocytes,or
immunofluorescence microscopy.

15. DIAGNOSIS
Shell Viral Culture (SVC):-This approach involves propagation of
viruses in mammalian cells grown in small vials or shell vials,
followed by staining with influenza virus-specific fluorescent
monoclonal antibodies
Immunofluorescence assays
Direct Fluorescent Antibody Test (DFA):-it is an antigen-based
test which involves direct staining of respiratory epithelial cells
derived from nasopharyngeal swabs or nasopharyngeal
aspirates with fluorescently labeled influenza virus-specific
antibodies followed by examination under a fluorescent
microscope.examples are D3 FastPoint L-DFA test & Bartels
Viral Respiratory Screening and Identification Kit

16. DIAGNOSIS
Serological assays
Hemagglutination Inhibition Assay:-is based on the ability of HA-
specific antibodies to prevent attachment of the influenza virus
(approx) four hemaggulutinating units) to erythrocytes obtained from
either chicken, turkey, human, horse, or guinea pigs.
Others include
Virus Neutralization Assay
Single Radial Hemolysis
Complement Fixation
Enzyme Linked Immunosorbent Assay

17. DIAGNOSIS
Rapid Influenza Diagnostic Tests (RIDTs):-These tests use
monoclonal antibodies that target the viral nucleoprotein and employ either enzyme
immunoassay/immunochromatographic (l techniques.examples are RIDTs BinaxNOW
Influenza A&B test, Directigen EZ Flu A+B,QuickVue Influenza A+B, 3M Rapid Detection
Flu A+B etc.
Nucleic Acid-Based Tests (NATs):-They are based on PCR and detect virus-specific DNA or
RNA sequences/genetic material rather than viral antigens or antibodies they include reverse
transcriptase-PCR (RT-PCR), ligase chain reaction, sequencing-based tests (including
pyrosequencing, next generation sequencing (NGS)), DNA microarray-based tests,nucleic acid
sequencing-based amplification (NASBA), loop-mediated isothermal amplification-based assay
(LAMP), simple
amplification-based assay (SAMBA), transcription-mediated amplification, strand displacement
amplification, etc
N/b These tests are used to identify the presence of virus specific DNA/RNA but are not used for
cervical cancer screening.

18. PREVENTION AND CONTROL
Vaccination is the most effective means of preventing influenza and its
complications. Seasonal influenza vaccines are the best available protection
against influenza.Protection from the vaccine however only lasts for one flu
season. The influenza virus strains can change each year, so the vaccine has to
also change to cover the anticipated new influenza viruses. That’s why
protection needs updating every year.
effective ways to reduce the transmission of influenza include:-
 avoiding touching your eyes, nose, and mouth
 not sharing eating or drinking utensils
 staying away from work or school for as long as you have symptoms
 covering coughs and sneezes & avoiding close contact with sick
people which might occur as a result of hand shaking;

19. VACCINATION
• Intradermal flu vaccine
• Quadrivalent flu vaccine
• Cell based flu vaccine
• Flublok
• Fluad
Intradermal flu vaccine
The intradermal flu vaccine is a shot that is injected into the skin instead of
the muscle(approved fro adults 18yrs and above)

20. VACCINATION
Quadrivalent flu vaccine:-The Quadrivalent flu vaccine is designed to protect against four
different flu viruses; two influenza A viruses and two influenza B viruses.
•Shot can be given to children age 6 months
•Other shots can be given to children 3yrs and older
•Nasal spray vaccine is approved for people (2-49yrs)
Flumist is an example of a Quadrivalent flu vaccine that is sprayed into the nose to help
protect against influenza. It can be used in children, adolescents, and adults ages 2 through
49
Cell based flu vaccine:- A cell-based flu vaccine is made by growing viruses in animal cells,
which is a different manufacturing process than the traditional egg-based manufacturing
process that is used to produce most flu vaccines.(approved for people(4yrs and older)

21. VACCINATION
Fluad:-A standard 3-dose trivalent inactivated flu vaccine,that contains an
adjuvant.Adjuvants help create a strong immune response to
vaccination.(Fluad is licensed only for persons aged 65 yrs and older.
Flublok:-it is a trivalent influenza vaccine that has been FDA approved for
use in adults 18 years and older.

22. TREATMENT
Neuraminidase inhibitors
They prevent viruses from budding (releasing) and spreading. They
may also reduce the spread of influenza viruses throughout the
respiratory tract and allow upper respiratory tract mucus to inactivate
the viruses more easily. examples are Zanamivir (Relenza®) and
Oseltamivir (Tamiflu®) which is indicated for the treatment of
uncomplicated acute illness due to influenza infection in patients aged
1 year and older, who have been symptomatic for no more than 2 days.
Zanamivir is indicated for the treatment of uncomplicated acute illness
due to influenza infection in patients aged 7 years and older and who
have been symptomatic for no more than 2 days.

23. TREATMENT
M2 channel inhibitors (Adamantanes)
They target the M2 ion channel of Influenza virus A and block it, this
prevents viral RNA and core proteins from being released and as a
result no replication, however resistance to the
Adamantanes can be achieved by just a single amino acid change in
M2.This prevents blocking and replication can continue because of this,
current guidelines do not recommend the
use of adamantanes especially due to widespread resistance since the
beginning of the 21st century
Examples:-Rimantadine and amantadine

24. END