Transcript Influenza A virus

VIROLOGIA
Influenza
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Influenza
The virus and its replication
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Influenza virus (Orthomyxovirus)
Genus
Orthomixovirus
Species
(* indicates type species)
Serotypes or Subtypes
H1N1, H1N2, H2N2, H3N1, H3N2, H3N8,
H5N1, H5N2, H5N3, H5N8, H5N9, H7N1,
H7N2, H7N3, H7N4, H7N7, H9N2, H10N7
Hosts
Influenza virus A
Influenza A virus (*)
Influenza virus B
Influenza B virus (*)
Human, seal
Influenza virus C
Influenza C virus (*)
Human, pig
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Human, pig,
bird, horse
Influenza A virus: HA subtypes
Subtype
Human
Swine
H1
.
.
H2
.
H3
.
Horse
Bird
.
.
.
.
.
H4
.
H5
.
H6
.
.
H7
.
H8
.
H9
.
H10
.
H11
.
H12
.
H13
.
H14
.
H15
.
H16
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.
Influenza virus nomeclature
HxNy (where 1 < x <16 and 1 < y < 9)
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Influenza virus (Orthomyxovirus)
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Influenza virus
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Influenza A virus genome RNA segments and coding assignments
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Influenza virus
life cycle
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Influenza A virus: attachment
•Binds to cell surface carbohydrate - sialic acid
•Ubiquitous receptor
•Can be present as part of glycoprotein or glycolipid
•Specific requirement for 2-3 and 2-6 linkages
gives different tropism for avian vs. human cells
(pigs have both)
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Influenza A virus: attachment
Specific preferences for receptors and/or linkages
gives different tropism for influenza viruses
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Influenza A virus: attachment
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Influenza A virus: entry
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Influenza A virus: uncoating
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Influenza A virus
transcription and replication
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Influenza A virus
transcription and replication
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Influenza A virus: maturation and budding
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Influenza
Pathogenesis
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20th century flu pandemics
Pandemic year
Year
Influenza virus
type
People infected
(approximate)
Estimated deaths
worldwide
Case fatality
rate
20-50 million
>2.5%
Spanish flu
1918-1919
A/H1N1
33% (500 milion)
Asian flu
1956-1958
A/H2N2
?
2 million
<0.1%
Hong Kong flu
1968-1969
A/H3N2
?
1 million
<0.1%
Seasonal flu
Every year
Mainly H3N2,
H1N1, and B
250,000-500,000
per year
<0.1%
5-15% (340
million-1 billion)
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Influenza virus: the infection
Influenza virus enters
through the nose and
settles in the
respiratory tract
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Influenza virus:pathogenesis
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Influenza virus: the disease features
• Incubation : 1- 4 days
• Prodromic phase: malaise, headache
• Disease’s symptoms: fever (3-8 days) , mialgia, cough
• The infection typically resolves within 7-10 days through
the action of the innate and acquired immune systems
• Complications:
» Pneumonia (viral),Pneumonia (bacterial),
Myosites, Encephalitises, Convulsions
» Reye Syndrome (treatment with aspirin)
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Influenza virus: the immune response
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Influenza
Epidemiology
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Antigenic variation of influenza virus envelope proteins
Antigenic drift
Is the appearance of a
virus with a slightly altered
surface protein (antigen)
structure following
passage in the natural
host. This process occurs
by accumulating
substitution mutations that
facilitate evasion of the
host immune response.
Antigenic shift
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Is a major change in the
protein of a virus as
completely new surface
proteins are acquired by
the virus. This process
occurs when viruses with
segmented genomes
exchange segments after
coinfection. The new
reassortant viruses display
dramatic changes in
surface proteins that
facilitate escape from
immune surveillance.
Influenza virus: the antigenic drift
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Influenza virus: the antigenic shift
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Generation of pandemic influenza virus strains
•A pandemic strain of influenza
may occur by genetic reassortment
between human and avian viruses,
or by adaptation of an avian virus.
•This may involve avian viruses
from aquatic birds or domestic
poultry, and could potentially
involve an additional species such
domestic pig.
•Reassortment
could
involve
simply the HA gene, both HA and
NA genes, or combinantion of HA
and other genes from the avian
virus
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Models for the generation of pandemic influenza virus strains
In the classical genetic reassortment model,
avian and human viruses bind their
respective receptors in the pig tracheal
epithelium
In the adaptation model, avian viruses
acquire the ability to replicate efficiently in
humans by adapting to the human receptor
in pigs. The change is mediated by a
mutation in the HA gene
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Models for the generation of pandemic influenza virus strains
An avian virus may infect a human and
reassort with a human virus
An avian virus may infect a human and
acquire the ability to recognize the receptor
on human epithelial cells, leading to efficient
replication in humans and the ability to
spread from human to human
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Eras of human Influenza A virus
The 1918 flu was H1N1
The 1957 “Asian flu” was H2N2
The 1968 “Hong Kong flu” was H3N2
The 1977 “Russian flu” was H1N1
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Postulated evolution of human influenza virus A from
1889 to 1977
Antigenic shift, not drift, was the driving force for the five pandemics of
human influenza during the past century
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Origins of the major human pandemic influenza virus strains
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Influenza
Prevention and control
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Every year, an estimated 3 million to 5 million people
worldwide become seriously ill from influenza, and as many
as 500,000 - primarily children and the elderly – die from the
ensuing complications.
Influenza virus infection: prevention
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2011-2012 Northern Hemisphere winter season
Flu vaccines are designed to protect against the three influenza viruses that
experts predict will be the most common during the upcoming season. Each
season, this includes an influenza B virus, an influenza A (H1N1) virus and an
influenza A (H3N2) virus. The composition of virus vaccines for use in the 20112012 Northern Hemisphere influenza season recommended by the World Health
Organization was:
* an A/California/7/2009 (H1N1)-like virus;
* an A/Perth/16/2009 (H3N2)-like virus;
* a B/Brisbane/60/2008-like virus.
The H1N1 strain used in this composition is the same strain used in the 2009 flu
pandemic vaccine.
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Influenza virus infection: therapy
Oseltamivir (Tamiflu)
Rimantadine (Flumadine)
Antiviral Drugs for the 2007-08 Flu Season:
Two flu antiviral drugs are recommended for use in the United States
during the 2007-08 flu season: oseltamivir and zanamivir.
Oseltamivir and zanamivir are effective against both influenza A and B
viruses.
Oseltamivir (Tamiflu) is approved to both treat and prevent flu in people
one year of age and older.
Zanamivir (Relenza) is approved to treat flu in people 7 years and older
and to prevent flu in people 5 years and older.
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Influenza virus infection: diagnosis
•
Virus isolation in primary cell cultures
•
Haemoadsorption on infected cells
•
Haemogglutination
•
Immunofluorescence
•
ELISA
•
RT-PCR
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Influenza
Avian flu
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Transmission electron micrograph of avian influenza H5N1 virus
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Avian influenza virus pathogenicity
All of the HPAI viruses belong to the H5 or
H7 subtypes
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Factors contributing to the emergence of pandemic H5N1 influenza
Factors of probable relevance
•The prevalence of an avian influenza virus subtype in
domestic poultry
•Documented human infection and human-to-human
transmission of the virus
Factors of unknown relevance
•High pathogenicity of the avian influenza virus
•The pathogenicity of the virus in mammals other than humans
•The ability of the viral haemagglutinin glycoprotein to bind to
sialic-acid residues with an -2,3-linkage (avian) or with an -2,6linkage (human)
•The stalk length of the viral neuraminidase glycoprotein
• The presence of a Lys627 instead of the Glu627 of the viral RNA
polymerase protein PB2 (polymerase basic protein 2) (high
virulence in mice)
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Generation of pandemic influenza H5 virus strains
•A pandemic strain of influenza H5
may occur by genetic reassortment
between human and avian viruses,
or by adaptation of an avian virus.
•This may involve avian viruses
from aquatic birds or domestic
poultry, and could potentially
involve an additional species such
domestic pig.
•Reassortment
could
involve
simply the HA gene, both HA and
NA genes, or combinantion of HA
and other genes from the avian
virus
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Affected areas with confirmed cases of H5N1 avian influenza
Overall mortality in reported H5N1 human cases is approximately 60%
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Cumulative Number of Confirmed Human Cases of Avian Influenza
A/(H5N1) Reported to WHO
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Phylogenetic relationships
of H5N1 viruses
Currently, there are ten different groups
(clades) of H5N1 viruses circulating
among poultry (clade 1 and clade 2
viruses). Clade 1 viruses have caused
human infections. At least three
subgroup or subclades of clade 2 H5N1
viruses have infected humans to date:
subclades 2.1, 2.2 and 2.3 viruses
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Prevention of pandemic H5N1 influenza
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Influenza
Pandemic H1N1 (swine flu) 2009
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The 2009 pandemic influenza H1N1 (swine flu) virus
Generation of pandemic 2009 H1N1 (swine flu)virus
2009 H1N1 influenza virus is a quadruple reassortment with gene products from pigs
(Europe and Asia origin), avian influenza and human influenza. This virus is antigenically
unrelated to H1N1 influenza viruses in circulation since 1957.
Host and lineage origins for the gene segments of the 2009 A (H1N1) virus
PB2, polymerase basic 2;
NP, nucleoprotein;
PB1, polymerase basic 1; PA, polymerase acidic;
NA, neuraminidase;
M, matrix gene;
HA, hemagglutinin;
NS, nonstructural gene
A maximum likelihood phylogenetic tree for nucleotide sequences of the
HA gene of selected influenza viruses
Pandemic 2009 H1N1 swine flu: deaths by august 2010
20th century flu pandemics
Pandemic year
Year
Influenza virus
type
People infected
(approx)
Estimated deaths
worldwide
Case fatality
rate
20-50 million
>2.5%
Spanish flu
1918-1919
A/H1N1
33% (500 milion)
Asian flu
1956-1958
A/H2N2
?
2 million
<0.1%
Hong Kong flu
1968-1969
A/H3N2
?
1 million
<0.1%
Seasonal flu
Every year
Mainly H3N2,
H1N1, and B
5-15% (340
million-1 billion)
250,000-500,000
per year
<0.1%
Swine flu
2009-2010
Pandemic A/H1N1
>622.482
(lab.confirmed)
14,286 (lab
confirmed)
0.03%
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Influenza stagionale:
8500 morti all’anno