Transcript Influenza A Virus

Viral Infections of the Respiratory Tract
Viral causes are the most common causes of upper
respiratory tract infections, including:
• Adenovirus (the most common viral cause)
• Rhinoviruses
• Influenza viruses
• Coronaviruses
• Enterovirus groups: Coxackieviruses A
(herpangina)
•Herpesviruses (rare): varicella zoster virus (VZV),
Eptein Barr virus (EBV), cytomegalovirus (CMV),
and herpes simplex virus (HSV-1)
Adenoviruses:
• Name originates from Greek word “adenas” which
means gland, site from which were initially isolated.
• Virions are icosahedral non-enveloped, 70-90 nm in
diameter with double stranded DNA genome.
• Fibers protruding from capsid facilitate binding on to
host
• 11 proteins are found in the
virion
• Genome encodes for up to
50 proteins
• Divided into 6 groups (A to F)
comprising 51 human serotypes
n
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Incubation period: 5 – 8 days
Transmission: Respiratory droplets, faecal- oral route, and
contact either by hand to eye or sexual.
Age affected: commonly among school-aged children
They cause latent infection in the tonsils, adenoids and
other lymphoid tissue.
Diagnosis:
• Isolation of the virus from the respiratory or eye discharge
or tissue culture.
• A fourfold or greater rise of antibody titre is a good
evidence of infection.
a
Clinical Picture:
1. Respiratory diseases: pharyngitis, rhinitis, laryngitis or
pneumonia
2. Acute respiratory disease (ARD)
among military recruits.
3. Eye infection: conjunctivitis or
keratoconjunctivitis
4. Pharyngo- conjunctival fever
5. Infantile gastroenteritis
6. Acute haemorrhagic cystitis
in children
Rhinovirus:
• Name originates from a Greek word means "nose“
• They cause common cold or acute bronchitis
• Picornoviridae family
• Virions are icosahedral
non-enveloped, single stranded
RNA virus
• Over 100 serotypes are
known
• Optimum growth occurs between
33 and 34 deg Celsius
• Not stable below the pH of 5-6
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Incubation period: 1 to 3 days (short)
Transmission: droplet infection or hand-to-hand contact
Multiplication of the virus: locally with no blood invasion
Affected age: All ages
The disease occurs sporadically or in epidemics.
Secondary bacterial infection may cause otitis media,
sinusitis, bronchitis or bronchpneumonia especially in
children.
Immunity is mainly superficial by IgA and interferon
(short term immunity).
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Clinical picture:
Human rhinoviruses are the primary cause of common
colds.
Symptoms include:
sore throat, runny nose, nasal
congestion, sneezing and
cough; sometimes
accompanied by muscle
aches,fatigue, malaise,
headache, muscle weakness,
or loss of appetite.
Influenza Virus:
• Orthomyxoviridae family
• They replicate in mucous membrane of upper and lower respiratory
tract
• They are helical, enveloped, single stranded RNA genome
• They are enclosed in a lipid envelop and a layer of glycoprotein
spikes known as haemagglutinin (HA) and neuraminidase (NA)
which are major antigenic determinants.
• They are divided into:
types A, B, C on the basis of the
nucleoprotein antigen
• Influenza occurs in epidemics and
pandemics
ORTHOMYXOVIRUSES
HA - hemagglutinin
NA - neuraminidase
helical nucleocapsid (RNA plus
NP protein)
lipid bilayer membrane
polymerase complex
M1 protein
type A, B, C : NP, M1 protein
sub-types: HA or NA protein
Role of H AND N Proteins
H = Hemagglutinin and N = Neuraminidase
Hemagglutinin allows the virus to bind to host cells
Neuraminidase helps the virus to release itself from
the highjacked cells in which it has reproduced
Influenza A Virus Constantly Changes
Antigenic drift
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Small changes in H or N proteins that occur from year to
year
Population is partially immune, but may be re-infected
over time (periodic epidemics)
Antigenic shift
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Acquisition of new H or N protein, possibly from an animal
virus
Population is not immune, everyone is susceptible
(pandemics)
Influenza A Virus:
Influenza A virus only is further classified into subtypes
based upon HA and NA antigens
16 HA subtypes and 9 NA subtypes are now recognized
circulating in birds, humans, swine and horses.
The most famous subtypes are:
A (H1N1): circulating in humans causing swine flu
A (H5N1): circulating in birds causing avian flu
Influenza B Virus:
Infects mammals only
Usually less severe illness
Clinical picture:
•Fever
•Headache
•Myalgia
•Cough
•Rhinitis
•Ocular Symptoms
Incubation period: 1 to 2 days
Transmission: droplet infection or hand-to-hand contact
Diagnosis:
1- Isolation of the virus from nose, throat swab
2- Tissue culture
3- Provisional - clinical picture + outbreak
Coronaviruses:
• Name originates from a Greek word meaning crown
because of the crown like appearance
of the surface projections.
• Family Coronaviridae
• They are large helical, enveloped,
single stranded RNA viruses
• The human coronaviruses (CoVs) are responsible for
about 30% of mild upper respiratory tract illness (common
cold)
• Newly emerged SARS-CoV causes severe acute
respiratory syndrome (SARS) that has been reported in
Asia, North America, and Europe.
SARS Disease:
Incubation period: 2 - 10 days
Transmission: droplet infection or contact to contaminated skin or fomites
Clinical Picture:
Fever, chills, rigors, headache, myalgia and malaise
Respiratory symptoms often begin 3-7 days after symptom onset and peak in the
second week.
Laboratory Diagnosis:
Serological Testing
 IFA: Indirect fluorescent antibody
 ELISA: Enzyme-linked immunosorbent assays
 Only for specimens obtained > 21 days by fever
Molecular Testing
 RT-PCR: Reverse transcriptase-PCR
 Can detect infection within the first 10 days
Culture: SARS-CoV (Vero E6 cell)
Herpesviruses:
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Icosahedral, enveloped double stranded DNA viruses.
Genome consisits of long and short fragments which may be
orientated in either direction, giving a total of 4 isomers.
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Three subfamilies:
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Alphaherpesviruses - HSV-1, HSV-2, VZV
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Betaherpesviruses - CMV, HHV-6, HHV-7
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Gammaherpesviruses - EBV, HHV-8
Set up latent or persistent infection following primary infection
Reactivation are more likely to take place during periods of
immunosuppression
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Both primary infection and reactivation are likely to be more
serious in immunocompromised patients.
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Herpesvirus Particle
HSV-2 virus particle.
Note that all herpesviruses
have identical morphology
and cannot be distinguished
from each other under
electron microscopy
Herpes Simplex Viruse Type 1 (HSV-1):
Double stranded DNA enveloped virus with a genome of around
150 kb
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The genome of HSV-1 and HSV-2 share 50 - 70% homology.
They also share several cross-reactive epitopes with each other.
There is also antigenic cross-reaction with VZV.
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Man is the only natural host for HSV.
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Transmission: By direct contact
Primary infections usually involves the mucous membrane of the
mouth
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Latency of HSV-1 is in trigeminal ganglia
Recurrent lesions manifest at any site innervated by the affected
neurons.
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HSV-1 Disease:
1.
Acute Gingostomatitis: the commonest classic presentation
2.
Recurrent herpes labialis (cold sores)
3.
Encephalitis
4.
Keratoconjunctivitis
5.
Disseminated infections:
e.g. pneumonia
Diagnosis:
1- Isolation of virus on tissue culture
2- Detection of HSV in vesicle fluid by electron microscopy
3- Detection of viral DNA by PCR
4- Detection of viral antigen by direct immunofluroescence or ELIZA
5- Serological diagnosis to detect IgM antibodies that indicates recent infection or
reactivation
HSV-1 Disease:
Cytopathic Effect of HSV in cell
culture: Note the ballooning of cells.
Positive immunofluorescence test
for HSV antigen in epithelial cell.
Varicella- Zoster Virus (VZV):
This virus causes 2 diseases:
(1) Chicken pox (Varicella):
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Infectious disease of children
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Characterized by fever and
vesicular rash
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Transmission: respiratory route
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Vesicles appear first on trunk
And then spread to face and extremities
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Recovery is the rule
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May be complicated with encephalitis
Varicella- Zoster Virus (VZV):
(2) Herpes Zoster (Shingles):
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Infectious disease of adults
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Characterized by painful
vesicular eruptions in areas of
skin supplied by sensory nerves
mainly thoracic & lumbar
or trigeminal nerve.
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Results from reactivation of latent varicella infection in the
neurons.
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May be complicate lymphoma, leukemia or immunosuppresion
Diagnosis of VZV:
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Virus Isolation: rarely carried out as it requires 2-3 weeks for a results.
Direct detection: electron microscopy may be used for vesicle fluids.
Immunofluorescense on skin scrappings can distinguish between the
two.
Serology: the presence of VZV IgG is indicative of past infection and
immunity. The presence of IgM is indicative of recent primary infection.
Cytopathic
Effect of
VZV in cell
culture:
Note the
ballooning
of cells.