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Paramyxoviruses and Rubella

Virus

Paramyxoviruses and Rubella Virus


Infections by paramyxoviruses and rubella virus are
common and cause highly contagious diseases in
children.
The paramyxovirus family contains viruses that
cause respiratory infections as well as systemic
disease like measles and mumps.
Rubella is caused by a togavirus.
Humans are the only reservoirs for these infections

Paramyxovirdae
Paramyxoviridae
Paramyxovirnae
Paramyxovirus genus
Parainfluenza viruses 1 and 3
Rubulavirus genus
Mumps, Parainfluenza viruses 2 and 4
Morbillivirus genus
Measles Virus

Pneumovirinae
Respiratory Syncytial Virus

Paramyxovirus Structure

Paramyxovirus Genome
RNA
Single stranded
Negative polarity
Single segment

6 - 10 genes, depending on virus type


Virion contains virus-encoded RNA-dependent
RNA polymerase

Paramyxovirus Attachment
Attachment Glycoproteins
Parainfluenzaviruses & Mumps Virus
HN (hemagglutinin/neuraminidase)
Receptor : sialic acid
Morbilliviruses (Measles)
H (hemagglutinin)
Receptor : CD46
Respiratory Syncytial Virus
G (glycoprotein)
Receptor : unknown

Paramyxovirus Penetration
F (fusion) glycoprotein
Penetration - direct fusion of virion envelope and
plasma membrane
F0 (precursor) - cleaved by cellular protease:
F0 > F1 + F2
F1 mediates fusion
Fusion of cells causes formation of syncytia (giant
multinucleated cells).
Because of fused cells, viruses are protected
against neutralizing antibody.

Paramyxovirus Replication
Occurs in the cytoplasm
Negative strand genome transcribed by virionassociated template
> mRNAs
> full-length positive strands (antigenome)
Full-length positive strands are templates for
progeny negative-strand genomes
Assembly of nucleocapsids in cytoplasm
Budding through the plasma membrane

PATHOGENESIS & IMMUNITY

Mild Upper Respiratory Illness


Parainfluenzaviruses 1, 2, 4
Pharyngitis
Tracheobronchitis

Croup
Parainfluenzaviruses 1, 2, 3

Laryngotracheobronchitis
Typically occurs in children (usually
under 5 years)
Characteristic cough and wheezing due to
swelling of larynx

Severe Lower Respiratory Tract Disease


Parainfluenzavirus 3
Typically occurs in infants
Bronchiolitis
Pneumonia

Respiratory Syncytial Virus (RSV)


Major cause of pneumonia and bronchiolitis in
infants under 6 months
Obstruction of the brochioles

Incubation period is short: 1 to 4 days


Especially high risk in infants with heart disease
or immunodeficiency
Croup, tracheobronchitis, mild U.R.T. in older
children, adults
Possibility of nosocomial infections of hospital staff

RSV: Pathogenesis and Prevention

1. Most common cause of acute, fatal


respiratory tract infections in infants.
2. Virtually everyone infected by age 3 years.

Transmission, Epidemiology, & Control

Yearly, winter

Clinical Disease:

Mumps
Caused by infection with Mumps Virus
Spread by close contact (saliva, aerosols)
Entry by Resp. Tract (?), replication in lymphoid
tissue, viremia
Approx. 18 - 21 day incubation, followed by
malaise, anorexia
Salivary gland infection, inflammation, swelling
(not all cases)
Males over 13 years may develop orchitis - painful
swelling of testicles

Mumps

ACUTE PAROTITIS (MUMPS)

Transmission, Epidemiology, Control & Prevent:

RUBEOLA
(MEASLES)

Measles: Facts:
1. 7th most frequent cause of death worldwide!!!
2. 40 million infected annually
3. 2 million deaths 3rd world countries & nonvaccinated in USA!!! 1/3 of American babies
not vaccinated!!!
4. Highly contagious - 95% of people in a
household will become infected.
5. Immunocompromised people Defect in
Cellular immunity - at very high risk, also!!

Measles Pathogenesis

Transmission by respiratory secretions


Initial replication in Upper Respiratory Tract
Infection of lymphoid tissues
Spread throughout the reticuloendothelial system
Secondary viremia spread virus to skin, resp. tract,
conjunctiva

Measles - Clinical Findings


Incubation period - about 9 to 11 days
Symptoms:
Fever, cough, coryza
Kopliks spots
Maculopapular rash
Conjunctivitis may occur

Severity related to nutritional status

Measles - Kopliks Spots

1 in 500 children in US who get the disease DIE!!!

CCC-P

SSPE: caused in three ways: 1. Direct neuronal infect.


2. Immune mediated (delayed) disease 3. Mutant
varient of the virus caused by acute infection.

Measles - Rash

Measles - Rash

Measles Complications

Bronchitis
Depresses Cell Mediated Immunity
Bacterial superinfection
Acute encephalomyelitis (rare: 1/1000 cases)
Subacute sclerosing panencphalitis (very rare:
1/300,000 cases)

PIE:

postinfectious encephalomyelitis

MIBE: measles inclusion body encephalitis


SSPE: subacute sclerosing panencephalitis

Transmission, Epidemiology, Control & Prevent:

Vaccines
MMR vaccine
Trivalent vaccine for Measles, Mumps and Rubella
Live attenuated vaccine
Subcutaneous administration

Monovalent vaccines also available


Older vaccines no longer recommended

Laboratory Diagnosis:

Slide 9.45

Rubella Virus
(German or 3-Day Measles, )

Pathogenesis of Rubella Virus Infections


Transmission by respiratory secretions
Systemic infection involving viremia
Can invade many different organs
Invades placenta and embryonic cells
Cell immune responses and circulating viral
immune complexes may be involved in
inflammatory responses (rashes and
arthritis)

Prodromal Rash on Palate in Rubella

Clinical Responses -Rubella (German or 3 day- measles)


Acute Infection
Incubation period is 16 days
Often subclinical infection
Mild fever and macular rash lasting 1-3 days
Complication of acute disease - temporary
arthritis

1.
2.

Rash
develops
If
mother
sero neg.

Clinical Responses -Rubella (German or 3 day- measles)


Congenital Rubella Syndrome

Acquired by transmission of virus through


placenta - mother may be asymptomatic
Causes severe malformations or death of
developing fetus
Occurs if pregnant women are infected during
first trimester
Expressed as chronic infection

Immunity and Diagnosis of Rubella Virus


Permanent immunity if disease acquired after 6
months of age
Presence of antibodies that inhibit
hemagglutination is a good indicator of
immunity and should be performed prior to
pregnancy to ascertain risk of congenital rubella.
Presence of Anti-Rubella IgM indicates recent
infection

Immunity and Control of Rubella Infections


MMR vaccine provides protection for at
least 18 years.
Should not be administered to pregnant
women.

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