Paramyxoviridae

For 3rd Year MLS Students

Prepared By Wondmagegn D.(MSC.)

Objectives
Explain the properties of Paramyxovirus
Describe the pathogenesis and clinical
Paramyxovirus infection
Illustrate epidemiology Paramyxovirus
Describe the diagnosis Paramyxovirus infection

features

Outline

Introduction
Structure and replication
PIV
Measles Virus
Mumps Virus
RSV

Introduction
Virion- Spherical, Pleomorphic, 150-300 nm
Enveloped virus : do not form such prominent spikes as on
influenza virus
2 glycoproteins : viral hemagglutinin (HN) and Fusion (F)
ss RNA, linear, non segmented, negative sense, 16-20 kb
Replication- cytoplasmic, bud from plasma membrane
They are similar in many respects to orthomyxoviruses but
are larger and do not have the segmented genome of the
influenza viruses .

Cont
The family Paramyxoviridae consists of three genera:
1. Paramyxovirus, which includes the parainfluenza viruses
and mumps virus;
2. Pneumovirus, which includes respiratory syncytial virus;
and
3. Morbillivirus, which includes the measles virus.
Their virions have similar morphologies and protein
components, and they share the capacity to induce cell-cell
fusion (syncytia formation and multinucleated giant cells).
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Cont
Table 59-1

Recent Classification

GENUS

GLYCOPROTEINS

TYPICAL MEMBERS

PARAMYXOVIRUS SUBFAMILY

Paramyxovirus

HN, F

HPIV1, HPIV3

Rubulavirus

HN, F

HPIV2, HPIV4, mumps virus

Morbillivirus

H, F

measles virus

Pneumovirus

G, F

respiratory syncytial virus

Metapneumovirus

G, F

metapneumoviruses

PNEUMOVIRUS SUBFAMILY

Cont
These agents cause some well-known major diseases.
Measles virus causes a potentially serious generalized
infection characterized by a maculopapular rash ( rubeola).
Parainfluenza viruses cause upper and lower respiratory
tract infections, primarily in children, including pharyngitis,
croup, bronchitis, bronchiolitis, and pneumonia.
Mumps virus causes a systemic infection whose most
prominent clinical manifestation is parotitis.
RSV causes mild upper respiratory tract infections in
children and adults but can cause life-threatening
pneumonia in infants.
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Cont
Paramyxoviruses earlier grouped with Orthomyxoviruses
because of HA and NA activities but they do have the
following differences
RNA non segmented
RNA is RNase resistant
Transcription of viral RNA in cytoplasm
Fusion of virus with cell membrane
Genetic reassortment-rare

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Structure and Replication

Paramyxoviridae typically consist of a helical nucleocapsid,
surrounded by an envelope that contains two types of integral
membrane or envelope proteins.
The first, the HN protein (H stands for hemagglutinin, and N
for neuraminidase), is involved in the binding of the virus to a
cell; measles virus lacks the neuraminidase activity.
The second, the F protein (F stands for fusion), functions to
fuse viral and cellular membranes, thus facilitating virus entry
into the cytoplasm where viral replication occurs
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Cont
Envelope Glycoproteins
HN glycoprotein HN - hemagglutinin + neuraminidase
activities Parainfluenza viruses
Measles - referred to as H protein - no neuraminidase
activity;
RSV - G protein - neither activity.
FUSION (F) Protein infection and pathogenesis- fusion of
viral envelope with plasma membrane of host cell cell to
cell fusion

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Cont

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Cont
pleomorphic

HN/H/G glycoprotein
SPIKES
F glycoprotein
SPIKES
helical nucleocapsid (RNA plus
NP protein)

lipid bilayer membrane

polymerase
complex

M protein
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Virus

Fusion protein

Measles virus

mumps

RSV

Parainfluenza

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Replication
Replication of the paramyxovirus genome, takes place in the cytoplasm of
the host cell.
Virus attaches to host cell surface receptors through HN, H or G
glycoproteins.
Fusion with the plasma membrane; ribonucleocapsid is released in the
cytoplasm.
The RNA of the virus is translated into positive sense RNA through use
of the enzyme RdRp, which is short for RNA-dependent-RNApolymerase.
The positive sense RNA can then act as mRNA which is read by the host
cell, and the host cells mechanisms build the necessary proteins, as well
as gets copied into more negative sense RNA to use in the daughter
virus.
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Cont

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Cont

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Parainfluenza virus
Viruses that usually cause mild cold like symptoms but can
also cause serious respiratory tract disease.
Four serologic types within the parainfluenza genus are
human pathogens.
Serologic types 1, 2,and 3 are second only to RSV as
important causes of severe lower respiratory tract infection
in infants and young children. They are especially associated
with laryngotracheobronchitis (croup).
Type 4 causes only mild upper respiratory tract infection in
children and adults.
limited to U.R.T. (no viremia)
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Cont
Transmission
Aerosols-Person to person contact

IP 2-6 days
Wide distribution

Type 3 most prevalent- pneumonia infants

Type 1 and 2 croup infants

Most children get infection-no serologic variation-rare

infection in adults.
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Pathogenesis
Infect epithelial cells of URT
The virus replicates more rapidly than measles and mumps
viruses and can cause giant cell formation and cell lysis.
Unlike measles and mumps rarely viremia
The viruses generally stay in the upper respiratory tract,
causing only cold like symptoms.
In approximately 25% of cases, the virus spreads to the
lower respiratory tract, and in 2% to 3%, disease may take
the severe form of laryngotracheobronchitis.
Death rare

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PIV Epidemiology
Parainfluenza viruses are ubiquitous, and infection is
common.
The virus is transmitted by person to person contact and
respiratory droplets.
Primary infections usually occur in infants and children
younger than 5 years.
Reinfections occur throughout life, indicating short-lived
immunity.
Type 3 most prevalent

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Clinical Manifestations
Croup
(laryngotraheobroncitis)
most
common
manifestation of parainfluenza virus infection. However other
viruses may induce croup e.g. influenza and RSV.
Other conditions that may be caused by parainfluenza
viruses
include
Bronchiolitis,
Pneumonia,
Flu-like
tracheobronchitis, and Corza-like illnesses.

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PIV Recovery
All infants- antibodies but not protective
Immunity short lived
Cell mediated immunity both cell damage and confers
protection
IgA protective but short lived
Antibodies to F Neutralize prevent cell to cell spread
Multiple serotypes and short live immunity
Reinfection more common milder

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Laboratory Diagnosis
Detection of Antigen - a rapid diagnosis can be made by the detection
of parainfluenza antigen from nasopharyngeal aspirates and throat
washings.
Virus Isolation - Parainfluenza virus is isolated from nasal washings and
respiratory secretions and grows well in primary monkey kidney cells.
The presence of virus-infected cells in aspirates or in cell culture is
indicated by the finding of syncytia and is identified with
immunofluorescence.
Serology - a retrospective diagnosis may be made by serology. CFT
most widely used.
Rapid RT-PCR techniques are becoming the method of choice to detect
and identify parainfluenza viruses from respiratory secretions.
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Infected cell fusion caused by paramyxoviridae

Uninfected

Infected

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PIV Treatment
Ribavirin-promising-aerosol form
Experimental- killed virus vaccine-good antibody titer - no
protection.
Subunit vaccines and Live attenuated vaccine-intranasal
being tested.
Careful monitoring of the upper airway.

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Measles
Single serotype & Humans are the natural host
Measles virus causes a potentially serious generalized
infection characterized by a maculopapular rash (rubeola).
Measles, also known as rubeola, is one of the five classic
childhood exanthems, along with rubella, roseola, fifth
disease, and chickenpox.

Historically, measles was one of the most common and

unpleasant viral infections, with serious potential sequelae.
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Measles

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Clinical Syndromes
Measles is a serious febrile illness .
The incubation period lasts 7 to 13 days, and the prodrome
starts with high fever and CCC and Pcough, coryza,
conjunctivitis, and photophobia.
The disease is most infectious during this time.
After 2 days of prodromal illness, the typical mucous
membrane lesions known as Koplik spots appear.

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Measles rash

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Measles pathogenesis

FIGURE 59-4

FIGURE 59-3

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Laboratory Diagnosis
The clinical manifestations of measles are usually so
characteristic that it is rarely necessary to perform laboratory
tests to establish the diagnosis.
The measles virus is difficult to isolate and grow, although it
can be grown in primary human- or monkey-cell cultures.
Respiratory tract secretions, urine, blood, and brain tissue are
the recommended specimens.
It is best to collect respiratory and blood specimens during
the prodromal stage and until 1 to 2 days after the
appearance of the rash.
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Laboratory Diagnosis
Measles antigen can be detected in pharyngeal cells or
urinary sediment with immunofluorescence;
the measles genome can be identified by reverse
transcriptase polymerase chain reaction (RT-PCR) in either
of the aforementioned specimens.
Characteristic
cytopathologic
effects,
including
multinucleated giant cells with cytoplasmic inclusion bodies,
can be seen in Giemsa stained cells taken from the upper
respiratory tract and urinary sediment.
Antibody, especially immunoglobulin M (IgM), can be
detected when the rash is present.
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The MMR Vaccine

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MUMPS
Mumps virus is the cause of acute, benign viral parotitis
(painful swelling of the salivary glands).
H and N + fusion protein on envelope spikes
Humans are the natural host.
thermolabile
Mumps is rarely seen in countries that promote use of the
live vaccine, which is administered with the measles and
rubella live vaccines.

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Mumps clinical presentation

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Time course of Mumps infection

FIGURE 59-8

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LABORATORY DIAGNOSIS
Virus can be recovered from saliva, urine, the pharynx,
secretions from Stensens duct, and cerebrospinal fluid.
Virus is present in saliva for approximately 5 days after the
onset of symptoms and in urine for as long as 2 weeks.
Mumps virus grows well in monkey kidney cells, causing the
formation of multinucleated giant cells.
Clinical diagnosis can be confirmed by serologic testing. A
fourfold increase in the virus-specific antibody level or the
detection of mumps-specific IgM antibody indicates active
infection.
Enzyme-linked immunosorbent assay, immunofluorescence tests,
and hemagglutination inhibition can be used to detect the
mumps virus, antigen,or antibody.
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TREATMENT & PREVENTION

Vaccines provide the only effective means for preventing

the spread of mumps infection.

Antiviral agents are not available.

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Respiratory Syncytial Virus

Most important cause of pneumonia
bronchiolitis in infants
Fusion proteins- syncytia formation
Humans and chimpanzees- natural host
2 serotype: A & B
is a member of the Pneumovirus genus.

and

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 lacks hemagglutinin and neuraminidase activities.

It is the most common cause of fatal acute
respiratory tract infection in infants and young
children.
It infects virtually everyone by 2 years of age, and
reinfections occur throughout life, even among
elderly persons.
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LABORATORY DIAGNOSIS
RSV is difficult to isolate in cell culture.
The presence of the viral genome in infected cells and
nasal washings can be detected by RT-PCR techniques,
and
commercially available immunofluorescence and
enzyme immunoassay tests are available for detection
of the viral antigen.

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TREATMENT & PREVENTION

In otherwise healthy infants, treatment is supportive,
consisting of the administration of oxygen, intravenous fluids,
and nebulized cold steam.
Ribavirin, is administered by inhalation.
Passive immunization with anti-RSV immunoglobulin is
available for premature infants.
Infected children must be isolated.
No vaccine is currently available for RSV prophylaxis.

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Summary
Structure
Negative sense ssRNA genome, helical nucleocapsid, envelope with attachment protein
and F protein

Pathogenesis
Transmission in respiratory droplets and fusion of virus envelope via F protein with
plasma membrane of cells in the respiratory tract
Replication in cytoplasm, budding
Viremia except for RSV and PIV
innate and antibody response important; many symptoms from immune response: rash
in measles and swelling in mumps; PIV bronchitis and croup; RSV bronchiolitis and
pneumonia in infants
Sequelae in CNS for measles and mumps

Diagnosis
serology or nucleic acid
Measles Koplik spots; mumps swelling of parotid gland

Treatment/prevention
MMR live attenuated viral vaccine for measles and mumps, none for RSV or PIV

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