Paramyxoviruses
The family is divided into 3 genera:
- Paramyxovirus: Parainfluenzavirus 1-4; Mumps
- Pneumovirus: Respiratory Syncytial Virus (RSV)
- Morbillivirus: Measles; Canine Distemper Virus.
Parainfluenzaviruses and RSV produce acute respiratory diseases (c.f. influenza),
Morbilliviruses and Mumps systemic disease - diversity! They also differ from Orthomyxoviruses genetically - non-segmented genome with
little genetic variation (c.f. influenza).
Morphology:
Glycoproteins - do not form such prominent spikes as on influenza virus:
- HN - haemagglutinin + neuraminidase activities;
- Measles - referred to as H protein - no neuraminidase activity;
- RSV - G protein - neither activity.
- F - consists of 2 disulphide-linked subunits (F1 + F2) -
responsible for cell fusion + haemolytic function.
- Other proteins:
- The M (matrix) protein lines the inner surface of the envelope.
- NP - nucleoprotein.
- L and P - polymerase activity
To view a negatively-stained electron micrograph of paramyxovirus particles, click here - or here for material from
Cape Town.
Genome:
Non-segmented (-)sense RNA, 17-20kb. The linear arrangement of genes (6) are separated
by repeated sequences, a polyadenylation signal at the end of the gene, the intergenic
sequence GAA followed by a translation start signal at the beginning of the next gene.
Replication:
Very similar for all viruses in this group. Unlike influenza, all the action occurs in
the cytoplasm. However, the overall strategy very similar to influenza, although unlike
influenza, Paramyxovirus replication is resistant to actinomycin D.
A large excess of nucleocapsids are produced in infected cells, which form characteristic
cytoplasmic inclusion bodies. Syncytium formation is quite common (F glycoprotein).
Pathogenesis:
Parainfluenzaviruses 1-4:
Cause acute respiratory infections of man ranging from relatively mild influenza-like
illness to bronchitis, croup (narrowing of airways which can result in respiratory
distress) and pneumonia; common infection of children. Transmitted by aerosols, virus is
usually limited to U.R.T. (no viraemia). Infections of L.R.T. (e.g. in very young
children) lead to more serious symptoms. Little serological variation, therefore rare
infection in adults.
Mumps:
- Recognised by the ancient Greeks, virus first isolated in 1934. Haemagglutination is a
valuable assay technique for this virus. Humans are believed to be the only natural
reservoir for the virus (possibly primates). Transmission via saliva and respiratory
secretions; less infectious than measles/chickenpox - more adult cases. Typically causes
painful swelling of parotid glands 16-18 days after infection. This is preceded by primary
replication of the virus in epithelial cells of the U.R.T. and local lymph nodes, followed
by viraemia. In children, mumps is usually self-limited, but in adults (post-puberty) a
proportion of cases have more serous sequalae: orchitis (20-30% of males - rarely
resulting in sterility); meningitis, encephalitis, pancreatitis, myocarditis, nephritis -
<1% adult cases.
- Treatment: none (passive immunization has been used).
- Prevention: one invariant serotype therefore vaccines are viable - both
formalin-inactivated and live attenuated exist, the latter now being widely used- see
below.
Measles:
- One of the most infectious diseases known! >106 deaths p.a. in children in
the third world - now part of the W.H.O expanded programme of immunization. Childhood
infection almost universal, protection resulting from this is probably lifelong. Both man
and wild monkeys are commonly infected, but the virus can also infect rodents (in wild?).
In culture, produces characteristic intranuclear inclusion bodies and syncytial giant
cells. Transmission and initial stages of disease similar to mumps, but this virus can
also infect via the eye and multiply in the conjunctivae. Viraemia following primary local
multiplication results in widespread distribution to many organs.
Symptoms: After a 10-12 day incubation period, dry cough, sore throat,
conjunctivitis (virus may be excreted during this phase!!!), followed a few days later by
the characteristic
red, maculopapular rash and Koplik's spots - raised red spots with white centres in
the mouth. Towards the end of the disease, there is extensive, generalized virus infection
in lymphoid tissues and skin. Complications include bronchopneumonia and otitis media
(with or without secondary bacterial infections) (relatively common), and encephalitis
(~1:2000 cases). Subacute schlerosing pan encephalitis (SSPE) results from a rare (~1 :
3x105 cases of measles), chronic infection in which the virus multiplies in the
brain with the expression of a limited repertoire of virus genes, resulting in
neurodegenerative disease.
- Treatment: None
- Prevention: Both live and killed vaccines exist. Vaccination with the live
attenuated vaccine has been practiced in the US since the 1960's with a dramatic decline
in the incidence of the disease (210), but has only been used more recently in the UK.
Trivalent live attenuated vaccine (MMR) usually given - all of these viruses best avoided
during pregnancy!
- Medscape Article: "Genetic
Diversity of Wild-Type Measles Viruses: Implications for Global Measles Elimination
Programs"
RSV:
First isolated in 1956 and subsequently recognised as a major cause of L.R.T. disease
in infants and young children. Infects man, monkeys and some rodents with disease
production, but inapparent infections (resulting in spread of virus) may occur in many
mammals. In culture, causes characteristic syncytial masses - hence the name. Highly
infectious, transmission by respiratory secretions. Primary multiplication occurs in
epithelial cells of U.R.T. producing a mild illness. In ~50% children less than 8 months
old, virus subsequently spreads into the L.R.T. causing bronchitis, pneumonia and croup.
Has been suggested as a possible factor in cot death. Prevention: Currently no vaccine!
Also, infection does not result in lasting protection (c.f. mumps, measles) therefore
repeated infections ('colds') occur throughout life - usually without serious consequences
in adults.
© AJC 1998
