Transcript Orthomyxovirus_Paramyxoviru Family

Medical biology, microbiology,
virology, immunology department
ORTHOMYXOVIRUSES
PARAMYXOVIRUSES
By as. E.V. Pokryshko
Orthomyxovirus Family
The name myxovirus was originally applied
to influenza viruses. It meant virus with an
affinity for mucins.
A model of the influenza virion
Types: A, B, C
Influenza A:
In Birds
16 H variants
9 N variants
In Humans
3 H variants
(H1, H2, and H3)
2 N variants
(N1 and N2)
Subtypes: H1N1, H2N2,H2N3
Influenza Viruses:
Antigenic Shift
Avian
Reservoir
Human
virus
Avian
virus
Other
mammals?
Swine
New
Reassorted
virus
Influenza Viruses:
Antigenic Drift

Gradual accumulation of mutations
that allow the hemagglutinin to escape
neutralizing antibodies (Point mutation
in HA gene)

Epidemic strains thought to have
changes in three or more antigenic
sites
Pathogenesis and Pathology
The virus enters the respiratory tract in airborne
droplets. Viremia is rare. Virus is present in the
nasopharynx from 1-2 days before to 1-2 days after
onset of symptoms.
Inflammation of the upper respiratory tract
causes necrosis of the ciliated and goblet cells of the
tracheal and bronchial mucosa but does not affect
the basal layer of epithelium.
Interstitial pneumonia may occur with necrosis of
bronchiolar epithelium and may be fatal. The
pneumonia is often associated with secondary
bacterial invaders: staphylococci, pneumococci,
streptococci, and Haemophilus influenzae.
Clinical Findings
The incubation period is 1 or 2 days.
Chills, malaise, fever, muscular aches,
prostration, and respiratory symptoms may
occur. The fever persists for about 3 days;
complications are not common, but
pneumonia, myocarditis, pericarditis, and
central nervous system complications occur
rarely. The latter include encephalomyelitis,
polyneuritis, Guillain-Barre syndrome, and
Reye's syndrome (see below).
Influenza Vaccines




Whole virus vaccine: inactivated virus
vaccine grown in embryonated eggs; 7090% effective in healthy persons <65 years
of age, 30-70% in persons ≥65 years
Split virus vaccine: previously associated
with fewer systemic reactions among the
elderly and children <12 years
Subunit vaccine: composed of H and N
Live, attenutated influenza virus vaccines
under development
Influenza: Chemoprophylaxis
Amantadine and rimantadine: effective
against type A, but not type B, influenza
viruses; block the M2 ion channel
 70-90% effective in preventing illness
 Administered to individuals at high risk of
complications who are vaccinated after
outbreak of infection, persons with
immune defficiency

Influenza: Chemotherapy
Amantadine (adults and children ≥ 1 year)
and rimantadine (adults)
 Zanamivir and oseltamivir:
neuraminidase inhibitors active against
both type A and B influenza viruses
 Reduce duration of illness by ~1 day when
administered within 2 days of the onset of
illness (uncomplicated influenza)

Laboratory Diagnosis
Throat washings or garglings are obtained
within 3 days after onset and should be tested at
once or stored frozen. Penicillin and streptomycin
are added to limit bacterial contamination.
For rapid detection of influenza virus in clinical
specimens, positive smears from nasal swabs may
be demonstrated by specific staining with
fluorescein-labeled antibody.
Paired sera are used to detect rises in HI, CF,
or Nt antibodies.
Family Paramyxoviridae
Genes:
Morbillivirus – measles virus,
Respirovirus – parainfluenza virus
(serotypes 1 and 3)
Rubulavirus - mumps virus,
parainfluenza virus
2, 4а, 4b),
Pneumovirus – RS-virus
(serotypes
PARAMYXOVIRUSES
pleomorphic
HN/H/G glycoprotein
SPIKES
F glycoprotein
SPIKES
helical nucleocapsid (RNA minus
NP protein)
lipid bilayer membrane
polymerase complex
M protein
STRUCTURE-PARAMYXOVIRUSES
Cell fusion. In the course of infection, paramyxo-
viruses cause cell fusion, long recognized as giant cell
formation.
MUMPS (Epidemic Parotitis)
Mumps is an acute contagious disease
characterized
by
a
nonsuppurative
enlargement of one or both of the parotid
glands, although other organs may also be
involved.
Properties of the Virus: The mumps virus
particle has the typical paramyxovirus
morphology. Typical also are the biologic
properties of hemagglutination, neuraminidase,
and hemolysin.
Epidemiology
The disease reaches its highest incidence in
children age 5-15 years, but epidemics occur
in army camps.
Humans are the only known reservoir of
virus.
The virus is transmitted by direct contact,
airborne droplets, or fomites contaminated
with saliva and, perhaps, urine. The period of
communicability is from about 4 days before
to about a week after the onset of symptoms.
Pathogenesis and Pathology
The virus travels from the mouth to the
parotid gland, where it undergoes primary
multiplication. This is followed by a generalized
viremia and localization in testes. ovaries,
pancreas, thyroid, or brain.
The ducts of the parotid glands show
desquamation
of
the
epithelium,
and
polymorphonuclear cells are present in the
lumens. There are interstitial edema and
lymphocytic infiltration.
Orchitis
PARAINFLUENZA VIRUS
The
parainfluenza
viruses
are
paramyxoviruses with morphologic and biologic
properties typical of the genus.
They grow welt in primary monkey or human
epithelial cell culture but poorly or not at all in
the embryonated egg. They produce a minimal
cytopathic effect in cell culture but are
recognized by the hemadsorption method.
Laboratory diagnosis may be made by the HI,
CF, and Nt tests.
PIV STRUCTURE
MEASLES (Rubeola)
Measles is an acute, highly infectious
disease
characterized
by
a
maculopapular
rash,
fever,
and
respiratory symptoms.
Properties of the Virus: Measles
virus is a typical paramyxovirus. It
lacks neuraminidase activity.
Measles virus
Pathogenesis and Pathology
Infection is contracted by inhalation of droplets
expelled in sneezing or coughing. Measles is spread
during the catarrhal prodromal period; they are
infectious from 1-2 days prior to the onset of symptoms
until a few days after the rash has appeared
The virus enters the respiratory tract, enters cells,
and multiplies there. During the prodrome, the virus is
present in the blood, throughout the respiratory tract,
and
in
nasopharyngeal,
tracheobronchial,
and
conjunctival secretions. It persists in the blood and
nasopharyngeal secretions for 2 days after the
appearance of the rash. Transplacental transmission of
the virus can occur.
Pathogenesis and Pathology
Koplik's spots are vesicles in the mouth formed
by focal exudations of serum and endothelial
cells, followed by focal necrosis. In the skin the
superficial capillaries of the corium are first
involved, and it is here that the rash makes its
appearance.
Generalized
lymphoid
tissue
hyperplasia occurs. Multinucleate giant cells are
found in lymph nodes, tonsils, adenoids, spleen,
appendix, and skin. In encephalomyelitis, there
are
petechial
hemorrhages,
lymphocytic
infiltration, and later, patchy demyelination in the
brain and spinal cord.
Koplik's spots
RESPIRATORY SYNCYTIAL (RS)
VIRUS
This labile paramyxovirus produces a
characteristic syncytial effect, the
fusion of cells in human cell culture. It is
the single most serious cause of
bronchiolitis and pneumonitis in infants.
Properties of the Virus: RS virus does
not hemagglutinate.
RSV- Structure
immunofluoresent stain
RSV- syncytium formation
Pathogenesis and Pathology
This disease is transmitted by coughing,
sneezing, sharing wash cloths towels and
other things with someone with RSV.
This disease is
extremely serious
when it comes to
children and infants
under the age of 3 and
elders.
This disease can result
in death.
Symptoms for this disease are: sneezing, runny
nose, sore throat, low fever, common cold
symptoms just more severe.
Treatment:
Supportive
Fluids, oxygen,
respiratory support,
bronchodilators
Antiviral Agents
Ribavirin (Virazole), a
synthetic guanosine
analogue, given as an
aerosol
RSV Bronchiolitis- clinical features
Prophylaxis
 Combination
live
virus
(measles-mumps-rubella)
vaccines
 Live attenuated measles virus vaccine
effectively prevents measles.