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Prepared by- sruthi
Acquaintance
negative-sense single- stranded RNAvirus -
orthomyxoviridae family.
It causesInfluenza diseasecommonly
known as‘Flu’.
highly contagious viral infection
 respiratory passagesof birds and mammals
including humanbeingscausingepidemics.
It isthe most familiar virus in thispresent
world.
Orthomyxoviridae
Order : Mononegavirales
medium sized(80-120 nm), pleomorphic, enveloped
Genome: linear, segmented (6-8), (-)sense, single-
stranded RNA,10-13.6 kb
It hassix genera, including genera:-
 InfluenzavirusA
 Influenzavirus B
 Influenzavirus C
 causerespiratory illness with systemicsymptoms.
History
Theword ‘Influenza’ comesfrom Italian languagemeans
‘to influence’ that wasfirst used by J.Hugger in1703.
 Hippocrates first made accurate description on it.
In 1933 it discovered by the scientists:Christopher
Andrews, Wilson Smith, and Patrick Laidlaw.
Electron-Micrograph
Morphology
Influenza type A,Band Care similar in structure. Thoseare
roughly spherical of 80-120 nm in diameter but type-C may
occur asfilamentous.
Continued….
Theouter layer is the lipid membrane, spikesare
composed of glycoproteins: Hemagglutanin (HA) and
Neuraminidase (NA).
There present M2 protein embedded in lipidmembrane
and M1 protein beneath the lipidmembrane.
Thecomplete genome of Influenza is segmented into 8
fragments but 7 fragments in caseof Influenza C.Theretotal
11 genesare located in the genome encoded 11proteins.
 Thegenomic sizeis about 13.5 bp.
* HA and NA proteins determine the subtype of influenza virus.
Continued….
NA= Neuraminidase
HA= Hemagglutinin
NP= Neucleoprotein
NS1= Non-structural protein
NS2(NEP)=mediates the exportof
RNP-complexes from nucleus.
PB1, PB1-F2,PB2, PA=subunits of
viral RNApolymerase and are all
crucial for viral transcription and
replication.
M1= Matrix proteins formcapside.
M2= Proton-selective Ion-channel
Genome-organization
Variation
There are total 25 serotypes of Influenza: 16 HAand 9
NAvarieties.
InfluenzaA: most virulent human pathogen among
influenza viruses, wide host-range, highest serotypes;
causesevere diseaseincluding: Bird-flu(H5N1), Swine-
flu(H1N1), become pandemics!
Influenza B :mostly found in human and only two serotypes
present. Influenza Bdon’t causepandemics due to limited
host range.
Influenza C :It is milder and causeslesssevere disease.
Don’t become endemic and no subtypepresent.
Hemagglutinin
-Influenza virus surface
glycoprotein, cylinder-
shaped, consists of 549amino
acids.
-It has acentral alpha-helix coil
and three spherical headscontain
sialic acid bindingsites
-works in viral attachment with
sialic acid receptor and in fusionof
viral envelope with endosome.
-Thereare at least 18different HA
antigens. H18 discovered in2013.
Neuraminidase
-Influenza virussurface
glycoprotein
-It has 9different NAantigens
-enzymatically cleaves the sialic
acid groups from host cells, thus
promote entry andreplication.
-promotes the releaseof
progeny viruses
-Targetof antiviral drugs:
Zanamvir, Oseltamivir
Life-cycle
(Pathology)
Pathophysiology
Influenza virus caninfect both upper and lowerrespiratory tracts.
Sialic acid on epithelial cells are thereceptors.
Thetypical incubation period of influenza is 24 hours to 4 days
average: 2 days.
 Children's are more readily affected than adults.
Symptoms
 Fiver: 100°F to 104°F,canbe raised to 106°F
 Headache
Dry cough
runny nose, sore throat
Fatigue (tiredness)
Body achesand Myalgia
Transmission
Influenza canbe spread in three mainways:
Direct transmission: an infected person frequently touchtheir
nose, mouth or conjunctiva.
Virus-laden aerosols: coughing,
sneezing, speaking,normal breathing
all produce aerosols. A good sneeze
cangenerate up to 20,000
aerosols. Evenasingle droplet may
causeinfection. Droplet-nuclei
(1-4 µm) suspended in the airfor
long period and spreads the diseasemuch.
Indirect transmission: through contaminated objects:called
fomites, such astoys, doorknobs, light switchesetc.
Diagnosis
Isolation
-- Nose, throat swab
-- Tissueculture
 Serology
Rapid Test:‘Rapid Influenza diagnostic test’ is most
common done by swabbing nose and throat secretion.
* Albeit, different tests and experiments the symptoms associatedwith Influenza are most important tools to become
identified asan Influenza patient.
Call your doctorwhen:
Difficulty breathing or shortness ofbreath
 Pain or pressure in the chest orabdomen
 Dizziness
 Confusion
 Severe or persistent vomiting
T
reatments
It includes arange of medications andtherapies:-
Antiviral drugs:
a.Oseltamivir: serving ascompetitive inhibitor of the activity of viral
neuraminidase enzyme on sialic acid.
b.Zanamivir: works by binding to the active site of the
neuraminidase protein, rendering the influenza virus unableto
escapeits host cell.
c.M2 inhibitors: Theantiviral drugs suchas-Amantadine and
Rimantadine block aviral ion channel (M2 protein) and preventthe
virus from infectingcells.
Symptomatictreatments
CDC recommends persons suffering from Influenza:
 Stayat home
 Get plenty of rest
 Drink lots of liquids
 Don’t smoke and avoid alcohol
 Remainalert for emergency warningsigns
Vaccination
Annual vaccination for agiven year.
Eachseasonal vaccine contains three/four viral-strain
antigens:
Type A H1N1
Type B H3N2
TypeB strains
* CDC said that Flu vaccine is 61%effective and recommends flu
vaccination for all over 6months.
Side effect:
Thereis no severe side-effects of influenzavaccine.
Sometimes allergic reaction and increased cough,runny
nose, asthma are identified inchildrens.
Continued…
• Inactivated subunit(TIV/QIV)
– intramuscular
– trivalent or quardivalent
– split virus and subunit types(killed)
– duration of immunity 1 year or less
• Liveattenuated vaccine(LAIV)
– intranasal
– Trivalent
– live attenuated
– duration of immunity at least 1 year
Interferon
TheAlpha/Beta Interferon Receptor Provides Protection
against Influenza Virus Replication
IFN-gammatreatment at early stagesof influenza virus
infection protects mice from death in aNKcell-dependent
manner.
 Side-effects:
Fever
Malaise
Muscle pain
Fatigue
Prevention
• Get vaccinated each year
•Washing hands
• Covering nose and mouth while
coughing, sneezing
• Avoid touching nose, mouth, eyes
• Limited contact with sickpeople.
Antigenic Drift
Dueto the absenceof proofreading activity, the RNA-
dependent RNApolymerase copies the viral genome making
error roughly in every 10 thousand nucleotides (which is
the approximate length of the influenza vRNA).Hence, the
majority of newly assembled influenza virusesare
mutants, thus the antibody-binding sites becomechanged.
Thisis called antigenic-drift.
 causedby point mutation
 change in HAand NA
 results in epidemics
 eg. outbreak of influenza AH3N2 (2003-2004)
 occurs in all type A, Band C
Continued…
AntigenicShift
When more than one type of influenza virus infects a
single cell the separation of viral genome into eight
separated segments allows mixing or reassortment of
new viral RNAsthat induces new strains of influenza
virus. Thisprocess called antigenic-shift. It occurs onlyin
influenza TypeA.
 causedby exchange of genetic materials (RNA)
 new strains generate
 results in pandemics
 eg.Asian flu by H2N2subtype in 1958-1959.
 only in influenza typeA
Continued…
Pandemic (Influenza)
Name ofPandemic Date Deaths
Spanish flu 1918-1920 20-100 million
Asian flu 1957-1958 1-1.5 million
Hong Kongflu 1968-1969 .75-1.0 million
Russian flu 1977-1978 No accuratecount.
2009flu pandemic 2009-2010 18,000
Influenza A (H1N1) pandemic:2009
.
Pandemic:2009
TheH1N1resulted when aprevious triple reassortment of
bird, swine and human flu viruses further combined with a
Eurasian pig flu virus and spreads out Swineflu.
Theoutbreak wasfirst detected in Mexico City on 18March
2009
 Total 14,286 people have been died worldwide.
U.S.president BarackObamabeing vaccinated against H1N1 flu on 20 December
2009
Current-Research
• Influenza Genome Sequencing Project(IGSP):
creating alibrary of influenza sequencesto clarify which factors makeone strain
more lethal than another.Asof mid-2008, over3000 isolates had been completely
sequenced.
• Research into new vaccines:
the generation ofnew vaccine strains . Themost remarkable is:
research on auniversal influenzaA
vaccine, targeted against the M2 protein
is being done at the University of Ghent
by Walter Fiers,Xavier Saelensand
their team and now under clinicaltrials.
• Study the infection inother
animals especially birds.
Avian flu
*Avian influenza known asbird-flu. All knownviruses
that causeinfluenza in birds belong to the species
influenza A virus.
*Most highly pathogenic strain H5N1 had beenspreading
throughout Asiasince 2003 and reached to Europe
In 2005.
*There are many
subtypes of AIV:
H5N1, H7N3, H7N7
H7N9, and H9N2
Swineflu
*Swine flu also known as‘Pig influenza’. It is causedbySwine
influenza viruses including Influenza Cand Influenza A
subtypes: H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3.
*Direct transmission of an influenza virus from pigs to humans is
occasionally possible.
*In 2009, aswine-origin
H1N1virus strain
commonly referred toas
"swine flu" causedthe
‘2009 flu pandemic’.
Fluin Bangladesh
Institute of Epidemiology, DiseaseControland
Research(IEDCR),ICDDRB,CDC(Bangladesh
branch) are disease monitoring arm.
Bangladesh notified its first infection on May22,
2008
Four flu viruses –H1N1, H5N1, H3N2and
H9N2—are circulating in Bangladesh.

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influenza-copy-BSC.pptx

  • 2. Acquaintance negative-sense single- stranded RNAvirus - orthomyxoviridae family. It causesInfluenza diseasecommonly known as‘Flu’. highly contagious viral infection  respiratory passagesof birds and mammals including humanbeingscausingepidemics. It isthe most familiar virus in thispresent world.
  • 3. Orthomyxoviridae Order : Mononegavirales medium sized(80-120 nm), pleomorphic, enveloped Genome: linear, segmented (6-8), (-)sense, single- stranded RNA,10-13.6 kb It hassix genera, including genera:-  InfluenzavirusA  Influenzavirus B  Influenzavirus C  causerespiratory illness with systemicsymptoms.
  • 4. History Theword ‘Influenza’ comesfrom Italian languagemeans ‘to influence’ that wasfirst used by J.Hugger in1703.  Hippocrates first made accurate description on it. In 1933 it discovered by the scientists:Christopher Andrews, Wilson Smith, and Patrick Laidlaw.
  • 6. Morphology Influenza type A,Band Care similar in structure. Thoseare roughly spherical of 80-120 nm in diameter but type-C may occur asfilamentous.
  • 7. Continued…. Theouter layer is the lipid membrane, spikesare composed of glycoproteins: Hemagglutanin (HA) and Neuraminidase (NA). There present M2 protein embedded in lipidmembrane and M1 protein beneath the lipidmembrane. Thecomplete genome of Influenza is segmented into 8 fragments but 7 fragments in caseof Influenza C.Theretotal 11 genesare located in the genome encoded 11proteins.  Thegenomic sizeis about 13.5 bp. * HA and NA proteins determine the subtype of influenza virus.
  • 8. Continued…. NA= Neuraminidase HA= Hemagglutinin NP= Neucleoprotein NS1= Non-structural protein NS2(NEP)=mediates the exportof RNP-complexes from nucleus. PB1, PB1-F2,PB2, PA=subunits of viral RNApolymerase and are all crucial for viral transcription and replication. M1= Matrix proteins formcapside. M2= Proton-selective Ion-channel
  • 10. Variation There are total 25 serotypes of Influenza: 16 HAand 9 NAvarieties. InfluenzaA: most virulent human pathogen among influenza viruses, wide host-range, highest serotypes; causesevere diseaseincluding: Bird-flu(H5N1), Swine- flu(H1N1), become pandemics! Influenza B :mostly found in human and only two serotypes present. Influenza Bdon’t causepandemics due to limited host range. Influenza C :It is milder and causeslesssevere disease. Don’t become endemic and no subtypepresent.
  • 11. Hemagglutinin -Influenza virus surface glycoprotein, cylinder- shaped, consists of 549amino acids. -It has acentral alpha-helix coil and three spherical headscontain sialic acid bindingsites -works in viral attachment with sialic acid receptor and in fusionof viral envelope with endosome. -Thereare at least 18different HA antigens. H18 discovered in2013.
  • 12. Neuraminidase -Influenza virussurface glycoprotein -It has 9different NAantigens -enzymatically cleaves the sialic acid groups from host cells, thus promote entry andreplication. -promotes the releaseof progeny viruses -Targetof antiviral drugs: Zanamvir, Oseltamivir
  • 14. Pathophysiology Influenza virus caninfect both upper and lowerrespiratory tracts. Sialic acid on epithelial cells are thereceptors. Thetypical incubation period of influenza is 24 hours to 4 days average: 2 days.  Children's are more readily affected than adults.
  • 15. Symptoms  Fiver: 100°F to 104°F,canbe raised to 106°F  Headache Dry cough runny nose, sore throat Fatigue (tiredness) Body achesand Myalgia
  • 16. Transmission Influenza canbe spread in three mainways: Direct transmission: an infected person frequently touchtheir nose, mouth or conjunctiva. Virus-laden aerosols: coughing, sneezing, speaking,normal breathing all produce aerosols. A good sneeze cangenerate up to 20,000 aerosols. Evenasingle droplet may causeinfection. Droplet-nuclei (1-4 µm) suspended in the airfor long period and spreads the diseasemuch. Indirect transmission: through contaminated objects:called fomites, such astoys, doorknobs, light switchesetc.
  • 17. Diagnosis Isolation -- Nose, throat swab -- Tissueculture  Serology Rapid Test:‘Rapid Influenza diagnostic test’ is most common done by swabbing nose and throat secretion. * Albeit, different tests and experiments the symptoms associatedwith Influenza are most important tools to become identified asan Influenza patient. Call your doctorwhen: Difficulty breathing or shortness ofbreath  Pain or pressure in the chest orabdomen  Dizziness  Confusion  Severe or persistent vomiting
  • 18. T reatments It includes arange of medications andtherapies:- Antiviral drugs: a.Oseltamivir: serving ascompetitive inhibitor of the activity of viral neuraminidase enzyme on sialic acid. b.Zanamivir: works by binding to the active site of the neuraminidase protein, rendering the influenza virus unableto escapeits host cell. c.M2 inhibitors: Theantiviral drugs suchas-Amantadine and Rimantadine block aviral ion channel (M2 protein) and preventthe virus from infectingcells.
  • 19. Symptomatictreatments CDC recommends persons suffering from Influenza:  Stayat home  Get plenty of rest  Drink lots of liquids  Don’t smoke and avoid alcohol  Remainalert for emergency warningsigns
  • 20. Vaccination Annual vaccination for agiven year. Eachseasonal vaccine contains three/four viral-strain antigens: Type A H1N1 Type B H3N2 TypeB strains * CDC said that Flu vaccine is 61%effective and recommends flu vaccination for all over 6months. Side effect: Thereis no severe side-effects of influenzavaccine. Sometimes allergic reaction and increased cough,runny nose, asthma are identified inchildrens.
  • 21. Continued… • Inactivated subunit(TIV/QIV) – intramuscular – trivalent or quardivalent – split virus and subunit types(killed) – duration of immunity 1 year or less • Liveattenuated vaccine(LAIV) – intranasal – Trivalent – live attenuated – duration of immunity at least 1 year
  • 22. Interferon TheAlpha/Beta Interferon Receptor Provides Protection against Influenza Virus Replication IFN-gammatreatment at early stagesof influenza virus infection protects mice from death in aNKcell-dependent manner.  Side-effects: Fever Malaise Muscle pain Fatigue
  • 23. Prevention • Get vaccinated each year •Washing hands • Covering nose and mouth while coughing, sneezing • Avoid touching nose, mouth, eyes • Limited contact with sickpeople.
  • 24. Antigenic Drift Dueto the absenceof proofreading activity, the RNA- dependent RNApolymerase copies the viral genome making error roughly in every 10 thousand nucleotides (which is the approximate length of the influenza vRNA).Hence, the majority of newly assembled influenza virusesare mutants, thus the antibody-binding sites becomechanged. Thisis called antigenic-drift.  causedby point mutation  change in HAand NA  results in epidemics  eg. outbreak of influenza AH3N2 (2003-2004)  occurs in all type A, Band C
  • 26. AntigenicShift When more than one type of influenza virus infects a single cell the separation of viral genome into eight separated segments allows mixing or reassortment of new viral RNAsthat induces new strains of influenza virus. Thisprocess called antigenic-shift. It occurs onlyin influenza TypeA.  causedby exchange of genetic materials (RNA)  new strains generate  results in pandemics  eg.Asian flu by H2N2subtype in 1958-1959.  only in influenza typeA
  • 28. Pandemic (Influenza) Name ofPandemic Date Deaths Spanish flu 1918-1920 20-100 million Asian flu 1957-1958 1-1.5 million Hong Kongflu 1968-1969 .75-1.0 million Russian flu 1977-1978 No accuratecount. 2009flu pandemic 2009-2010 18,000
  • 29. Influenza A (H1N1) pandemic:2009 .
  • 30. Pandemic:2009 TheH1N1resulted when aprevious triple reassortment of bird, swine and human flu viruses further combined with a Eurasian pig flu virus and spreads out Swineflu. Theoutbreak wasfirst detected in Mexico City on 18March 2009  Total 14,286 people have been died worldwide. U.S.president BarackObamabeing vaccinated against H1N1 flu on 20 December 2009
  • 31. Current-Research • Influenza Genome Sequencing Project(IGSP): creating alibrary of influenza sequencesto clarify which factors makeone strain more lethal than another.Asof mid-2008, over3000 isolates had been completely sequenced. • Research into new vaccines: the generation ofnew vaccine strains . Themost remarkable is: research on auniversal influenzaA vaccine, targeted against the M2 protein is being done at the University of Ghent by Walter Fiers,Xavier Saelensand their team and now under clinicaltrials. • Study the infection inother animals especially birds.
  • 32. Avian flu *Avian influenza known asbird-flu. All knownviruses that causeinfluenza in birds belong to the species influenza A virus. *Most highly pathogenic strain H5N1 had beenspreading throughout Asiasince 2003 and reached to Europe In 2005. *There are many subtypes of AIV: H5N1, H7N3, H7N7 H7N9, and H9N2
  • 33. Swineflu *Swine flu also known as‘Pig influenza’. It is causedbySwine influenza viruses including Influenza Cand Influenza A subtypes: H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3. *Direct transmission of an influenza virus from pigs to humans is occasionally possible. *In 2009, aswine-origin H1N1virus strain commonly referred toas "swine flu" causedthe ‘2009 flu pandemic’.
  • 34. Fluin Bangladesh Institute of Epidemiology, DiseaseControland Research(IEDCR),ICDDRB,CDC(Bangladesh branch) are disease monitoring arm. Bangladesh notified its first infection on May22, 2008 Four flu viruses –H1N1, H5N1, H3N2and H9N2—are circulating in Bangladesh.