ORTHOMYXOVIRUS INFLUENZA VIRUS - PowerPoint Presentation

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ORTHOMYXOVIRUS

INFLUENZA VIRUS

PROFF. M BANERJEE

MICRO.

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Myxovirus

Myxovirus

for a

gp

of envelop RNA viruses

charecterised

by their ability to adsorb onto

mucoprotrein

receptors on erythrocytes causing

hemagglutination

.

Name- affinity of the

vs

to

mucin

.

Classified into 2 separate family-

ORTHOMYXOVIRUS – Influenza

vs

PARAMYXOVIRUS -

Mumps,measles

,

parainfluenza

, respiratory

syncytial

Vs .

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DIFF BETWEEN ORTHO & PARAMYXOVIRUS

ORTHOMYXOVIRUS

PARAMYXOVIRUS

Size-

80 – 120 nm

Shape-

Spherical, filaments in fresh isolates

GENOME – segmented, 8 pieces of RNA. Diameter of neucleocapsid- 9nm Site of synthesis of Ribonucleoprotein -Nucleus

100-300 nm

Pleomorphic

Single linear molecule of RNA

18 nm

Cytoplasm

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Orthomyxovirus

Paramyxovirus

Genetic

reassortment

-

common

Dependent RNA Synthesis-

Required for multiplicationEffect of Actinomycin D- Inhibit multiplicationAntigenic Stability- Varaible Hemolysin- Absent

Absent

Not requires

Does not inhibit

Stable

Present

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INFLUENZA VIRUS

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Orthomyxoviridae

Order :

Mononegavirales

medium sized(80-120 nm), enveloped

Genome: linear, segmented (6-8), (-)sense, single stranded

RNA, 10-13.6 kb

It has six genera, including genera:-

Influenzavirus A Influenzavirus B Influenzavirus C cause respiratory illness with systemic symptoms.

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Influenza virus is a negative-sense

singlestranded

RNA virus under the

orthomyxoviridae

family.

It causes Influenza disease commonly

known as ‘Flu’.

Influenza is a highly contagious viral infection of the respiratory passages of birds and mammals including us can occur in epidemics. It is the most familiar virus in this present world.

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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),….

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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.

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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.

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History

The word ‘Influenza’ comes from Italian language means ‘to influence’ that was first used by J. Hugger in 1703.

Hippocrates first made accurate description on it.

In 1933 it discovered by the scientists: Christopher Andrews, Wilson Smith, and Patrick Laidlaw.

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Electron-Micrograph

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Morphology

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Influenza type A,B, and C are similar in structure. Those are roughly spherical of 80-120 nm in diameter but type-C may occur as filamentous

.

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The outer layer is the lipid membrane, spikes are

composed of

glycoproteins

:

Hemagglutanin

(HA) and

Neuraminidase (NA).

There present M2 protein embedded in lipid membrane and M1 protein beneath the lipid membrane.

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The complete genome of Influenza is segmented into 8 fragments but 7 fragments in case of Influenza C. There total 11 genes are located in the genome encoded 11 proteins.

The genomic size is about 13.5

bp

.

*

HA and NA proteins determine the subtype of influenza virus.

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NA= Neuraminidase

HA=

Hemagglutinin

NP=

Neucleoprotein

NS1= Non-structural protein

NS2(NEP)=mediates the export of

RNP-complexes from nucleus.

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PB1, PB1-F2, PB2, PA = subunits of

viral RNA polymerase and are all

crucial for viral transcription and

replication.

M1= Matrix proteins form

capside

.

M2= Proton-selective Ion-channel

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There are total 25 serotypes of Influenza: 16 HA and 9 NA varieties.

Influenza A: most virulent human pathogen among

influenza viruses, wide host-range, highest serotypes;

cause severe disease including: Bird-flu(H5N1),

Swineflu

( H1N1), become pandemics!

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Influenza B

: mostly found in human and only two serotypes

present. Influenza B don’t cause pandemics due to limited host range.

Influenza C

: It is milder and causes less severe disease.

Don’t become endemic and no subtype present.

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Hemagglutinin

-Influenza virus surface

glycoprotein, cylinder shaped,

consists of 549 amino

acids.

-It has a central alpha-helix coil and three spherical heads contain

sialic

acid binding sites

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Hemagglutinin

-works in viral attachment with

sialic

acid receptor and in fusion of viral envelope with

endosome

.

-There are at least 18 different HA

antigens. H18 discovered in 2013.-Potential target for antiviral drugs

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Neuraminidase

-

Influenza virus surface glycoprotein

-

It has 9 different NA antigens

-

enzymatically

cleaves the sialicacid groups from host cells, thus promote entry and replication.

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Neuraminidase

-

promotes the release of progeny viruses

-

Target of antiviral drugs:

Zanamvir

,

Oseltamivir

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Hemagglutinin

(HA)

is a

lectin

that mediates binding of the virus to target cells and entry of the viral genome into the target cell.

Neuraminidase (NA)

is involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles.

These proteins are targets for

antiviral drugs

.

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Pathophysiology

Influenza virus can infect both upper and lower respiratory tracts.

Sialic

acid on epithelial cells are the receptors.

The typical incubation period of influenza is 24 hours to 4 days with

average: 2 days.

Children's are more readily affected than adults.

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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

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Different species harbor different strains of the flu virus:

Human flu

Bird flu

Swine flu

………………

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Human Influenza

Human influenza virus

subtypes that spread widely among humans.

Human flu-causing

viruses can belong to any of three major influenza-causing

Orthomyxo

viruses; 

Influenza A; B; C virus

.

Three known A subtypes of influenza viruses currently circulating among humans

(H1N1, H1N2, and H3N2).

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Symptoms

Fiver: 100°F to 104°F, can be raised to 106°F

Headache

Dry cough

runny nose, sore throat

Fatigue (tiredness)

Body aches and

Myalgia

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Transmission

Influenza can be spread in three main ways:

Direct transmission: an infected person frequently touch their

nose, mouth or conjunctiva.

Virus-laden aerosols: coughing,

sneezing, speaking, normal breathing all produce aerosols. A good sneeze can generate up to 20,000

aerosols.

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Even a single droplet may cause infection. Droplet-nuclei (1-4

μm

) suspended in the air for long period and spreads the disease much.

Indirect transmission: through contaminated objects :called

fomites

, such as toys, doorknobs, light switches etc.

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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.

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Avian Influenza

Fifteen subtypes

of influenza virus are known to infect birds, thus providing an extensive reservoir of influenza viruses potentially circulating in bird populations.

H5N1;

the strain of avian flu known as has been behind outbreaks of deadly avian flu.

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Avian Influenza

Avian influenza transmitted by birds usually through feces or saliva.

Avian influenza is not usually passed on to humans, although it has been contracted by people who have handled infected birds or touched surfaces contaminated by the birds.

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Migratory water birds, especially wild ducks. They may do not show clinical disease. The virus colonizes the intestinal tract and is spread in the feces

. They act as a reservoir for the infection of other species

.

Pigs

can be infected by bird influenza (as well as by the form of influenza that affects humans) and can pass on the flu to humans.

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Swine Flu

Swine influenza (swine flu)

 is a respiratory disease of pigs caused by type A influenza virus that regularly cause outbreaks of influenza in pigs.

Like human influenza viruses, there are different subtypes and strains of swine influenza viruses. The main swine influenza viruses circulating in U.S. pigs in recent years are: H1N1 influenza virus, H3N2 virus, H1N2 virus.

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The Influenza A

Influenza A viruses are constantly changing, and they might adapt over time to infect and spread among humans.

All type A influenza viruses, including those that regularly cause seasonal epidemics of influenza in humans, are genetically labile and well adapted to elude host defenses.

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Influenza viruses lack mechanisms for the “proofreading” and repair of errors that occur during replication. As a result of these uncorrected errors, the genetic composition of the viruses changes as they replicate in humans and animals, and the existing strain is replaced with a new antigenic variant.

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Antigenic Drift

Due to the absence of proofreading activity, the

RNAdependent

RNA polymerase 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 viruses are mutants, thus the antibody-binding sites become changed.

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This is called antigenic-drift.

caused by point mutation

change in HA and NA

results in epidemics

eg

. outbreak of influenza A H3N2 (2003-2004)

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Antigenic Shift

Antigenic shift

is where there is a major change in the

genome

of the virus. This occurs as a result of recombination.

or

reassortment

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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 RNAs that induces new strains of influenza virus. This process called antigenic-shift. It occurs only in influenza Type A.

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caused by exchange of genetic materials (RNA)

new strains generate

results in pandemics

eg

. Asian flu by H2N2 subtype in 1958-1959.

only in influenza type A

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LABORATORY DIAGNISIS

DEMONSTRATION OF VIRUS ANTIGEN-

On the surface of nasopharyngeal cells by

immunofluorescence

test .

ISOLATION OF VIRUS –

First 2 or 3 days of illness. If not processed immedeately stored at 4 C, if delay , at -70 C .After appropriate treatment (by antibiotic/filtration) inoculate in eggs or monkey kidney cell culture.After harvesting fluid are tested for hemagglutination with guinea pig and fowl erythrocytes.

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Subtype identification done by

hemagglutination

inhibition test .

Rapid identification in infected cell culture by

Immunofluorescence

test.

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SEROLOGY

Compliment fixation test

Hemagglutination

inhibition test

Radial

immunodiffusion

test

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MOLECULAR

RT-PCR

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IMMUNITY

An attack- effective protection for 1 or 2 yrs.

Short duration due to antigenic variation.

Following infection with different variant of

inf

vs

, patient develop immunity to all infecting infl vs.

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IMMUNITY

And pt develop Abs not only the present infecting

Infl

Vs but to all which were previously infected, and predominantly against the strain which caused the earliest.

Viz

“original antigenic sin”

Local concentration of

of antihemagg Ab and anti neuraminidase Ab (mainly IgA) in resp tract -pretective

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Infection Control

Infection Control

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Vaccination

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Vaccination

www.fightflu.com

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Treatment

Treatment with

oseltamivir

(trade name

Tamiflu

®) or

zanamivir

(trade name Relenza®) is recommended for all people with suspected or confirmed influenza who require hospitalization.