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Orthomyxoviruses
80-120 nm, spherical
ssRNA, negative sense
Segmented (8) genome
Gen products:
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PB2: RNA polymerase; recognise the cap
PB1-F2: Propaoptotic activity
PB1: RNA pol., endonuclease, elongation
PA: RNA pol.; protease
HA: Surface GP, receptor binding, fusion; major antigen
NP: RNA binding, RNA synthesis, transport of RNA to nucleus
NA: Surface GP; neuraminidase activity
M1: MAtrix protein; export from nucleus; interaction with
vRNP surface glycoproteins; budding
M2: Membrane protein; ion channel activity; assembly
NS1: Multifunctional protein; agonist of viral IFN
NEP/NS2: Transport of vRNP from nucleus
Unique Features of the Influenza A and B Viruses
Enveloped virion has a genome of eight
unique negative-sense RNA nucleocapsid
segments.
•Hemagglutinin glycoprotein is the viral
attachment protein and fusion protein; it
elicits neutralizing, protective antibody
responses.
•Influenza transcribes and replicates its
genome in the target cell nucleus but
assembles and buds from the plasma
membrane.
Body_ID: B059001
The antiviral drugs amantadine and rimantadine
inhibit an uncoating step and target the M2
(membrane) protein for influenza A only.
•The antiviral drugs zanamivir and oseltamivir inhibit
the NA protein of influenza A and B.
•The segmented genome promotes genetic diversity
caused by mutation and reassortment of segments
on infection with two different strains.
•Influenza A infects humans, mammals, and birds
(zoonosis).
M1, M2 and NP are typespecific 
İnfluenza A, B, and C
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Strains of influenza A virus are classified by the
following four characteristics:
Type (A, B, and C)
Place of original isolation
Date of original isolation
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Antigen (HA and NA)
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Influenza A/New York/07/09
(H1N1)
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Mutations in HA and NA genes 
Antigenic drift
Reassorments  Antigenic shift
Pandemic
DAte
Pandemic
Severity
Index
Deaths
Subtype
Asiatic
1889–1890
(Russian) Flu
1 million
posible H2N2 ?
Spanish Flu 1918–1920
40 to 100
million
H1N1
5
Asian Flu
1957–1958
1 to 1.5
million
H2N2
2
Hong Kong
Flu
1968–1969
0.75 to 1
million
H3N2
2
Swine flu
2009-2010
H1N1
Disease Incidence
Pandemic
Pandemic
Interpandemic Period
Epidemic
Epidemic
Epidemic
1
2
3
4
5
6
7
8
Time in Years
9
10
11
12
Mean Population Antibody Level
Incidence of clinically manifest influenza
Mean level of population antibody vs A HxNx
Mean level of population antibody vs A HyNy
Introduction of Significant minor variation A HxNx may Introduction of hypothetical
hypothetical occur at any of these points. Epidemics A HyNy major (new subtype)
A HxNx virus may or may not be
variant A HxNx disappears
associated with such variations
Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases, 5th ed. 2000:1829.
Modified from Kilbourne ED. Influenza. 1987:274, with permission.
Dünya Sağlık Örgütü
Pandemi Uyarısı
Epithelial demage
()
No viremia
Acute influenza
Symptoms regress
(~ 5 day)
Onset of the symptoms
(1-5 days)
Viral Pneumonia
Viral shedding
5 -10 days
Sekonder Bakteriyel
Pnömoni/Komplikasyonlar
Common Diagnostic tests
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Rapid Antigen (EIA)
– Sensitivity: 60-80%
– Specificity: 90%
Culture (Shell Vial)
– Sensitivity: 70-80%
– Specificity: 100%
RT-PCR, multiplex RT, multiplex
PCR, array, luminex based
DFA
PARAMYXOVIRUSES
15 kb lineer, negative
sense RNA
Speherical to
plemorphic r > 150 nm
6 structutal proteins
Unique Features of the Paramyxoviridae
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Large virion consists of a negative RNA genome in a
helical nucleocapsid surrounded by an envelope
containing a viral attachment protein (hemagglutininneuraminidase [HN], parainfluenza virus and mumps
virus; hemagglutinin [H], measles virus; and
glycoprotein [G], respiratory syncytial virus [RSV])
and a fusion glycoprotein (F).
The three genera can be distinguished by the activities
of the viral attachment protein: HN of parainfluenza
virus and mumps virus has hemagglutinin and
neuraminidase, and H of measles virus has
hemagglutinin activity, but G of RSV lacks these
activities.
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Virus replicates in the cytoplasm.
Virions penetrate the cell by fusion with the
plasma membrane and exit by budding from
the plasma membrane.
Viruses induce cell-cell fusion, causing
multinucleated giant cells.
Paramyxoviridae are transmitted in
respiratory droplets and initiate infection in
the respiratory tract.
Cell-mediated immunity causes many of the
symptoms but is essential for control of the
infection.
Measles virus
Parainfluenzaviruses
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♦ PIV types 1 and 2 most often cause outbreaks of croup in
autumn/early winter, with an alternate year pattern. PIV-1 tends
to attack children ages 2-6 years.
♦ PIV-3 causes croup less commonly than PIV-1 and 2. Infections
are sporadic and year-round, including spring and summer.
Primary infection with PIV 3 in young infants and children <2
years of age is a fairly common cause of bronchiolitis and
pneumonia.
♦ PIV-4 infections, even primary infections, are usually milder
and are generally associated with mild URI symptoms.
♦ Particularly severe and persistent infections are known to
occur in immunocompromised children and adults; prolonged
viral shedding is seen.
Mumps virus
Respiratory syncytial
virus
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RSV A
RSV B
November-May epidemics
Metapneumovirus
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First described in 2001
Widespread; seropositivity among
young adults and older people 100%
Smilar disaese as RSV
Between Decembre and April
Among young children less common
compared to RSV
Henipaviruses
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Hendra and Nipah viruses
Zoonotic viruses (fruit bats)
Endemic – Australasia
Nipah virus  Malaysia encephalitis
(from pigs)
Hendra  Australia (equine virus)
Togaviridae and
Flaviviridae
Rubella
Togaviridae
Rubivirus
Positive sense SS RNA
70 nm
9 genotypes
Incubation period: 12 days
and longer
Viremia: Devopes after 7-9
days and lasts till appearence
of rush but viral shedding
continues
20-50% subclinical
Rush
facetrunkextremities
< 3 days
In adults (esp. Women
transient arthralgia)
Rarely thrombocytopenic
pupura and encephlaitis
Epidemics every 6-10 years
Explosive epidemics every
20-25 years
In first semester 85%
In second semester 15%
Intrauterine infection  viral persistance
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positive-strand RNA
27–33 kb
3′ structural proteins, including spike
(S), envelope (E), membrane (M) and
nucleocapsid (N)
NS: replicase protein (ORF1 and 2)
Human Coronavirus
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Group 1: Transmissible gastroenteritis virus (TGEV),
porcine epidemic diarrhea virus (PDEV), feline
infectious peritonitis virus (FIPV), canine
coronavirus and HCoV-229E, HCoV-NL63
Group 2: Mouse hepatitis virus (MHV), bovine
coronavirus, haemagglutinating encephalomyelitis
virus, HCoV-HKU1 and HCoV-OC43; bat SARSCoV and SARS-CoV considered distantly related
Group 2b coronaviruses.
Group 3: Avian coronaviruses