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.

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.


? Probable Human Infection with a Newly Described Virus in the Family Paramyxoviridae ?



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