Paramyxoviruses

Paramyxoviruses
The paramyxoviruses include the most important agents of respiratory infections of infants and young children (respiratory syncytial virus and the parainfluenza viruses) as well as the causative agents of two of the most common contagious diseases of childhood (mumps and measles). The World Health Organization estimates that acute respiratory infections and pneumonia are responsible every year worldwide for the deaths of 4 million children under 5 years of age. All members of the Paramyxoviridae family initiate infection via the respiratory tract. Replication of the respiratory pathogens is limited to the respiratory epithelia, whereas measles and mumps become disseminated throughout the body and produce generalized disease.
Properties of Paramyxoviruses can be summarized as following:



Virion: Spherical, pleomorphic, 150 nm or more in diameter (helical nucleocapsid, 13–18 nm) 
Composition: RNA (1%), protein (73%), lipid (20%), carbohydrate (6%) 
Genome: Single-stranded RNA, linear, nonsegmented, negative-sense, noninfectious, about 15 kb 
Proteins: Six to eight structural proteins 
Envelope: Contains viral glycoprotein (G, H, or HN) (which sometimes carries hemagglutinin or neuraminidase activity) and fusion (F) glycoprotein; very fragile 
Replication: Cytoplasm; particles bud from plasma membrane 
Outstanding characteristics: 
  Antigenically stable
  Particles are labile yet highly infectious










Characteristics of Genera in the Subfamilies of the Family Paramyxoviridae.



  Paramyxovirinae Pneumovirinae
Property Respirovirus  Rubulavirus  Morbillivirus  Henipavirus1
  Pneumovirus  Metapneumovirus 
Human viruses Parainfluenza 1, 3 Mumps, parainfluenza 2, 4a, 4b Measles Hendra, Nipah Respiratory syncytial virus Human metapneumovirus
Serotypes 1 each 1 each 1 ? 2 ?
Diameter of nucleocapsid (nm) 18 18 18 ? 13 13
Membrane fusion (F protein) + + + + + +
Hemolysin2
  + + + ? 0 0
Hemagglutinin3
  + + + 0 0 0
Hemadsorption + + + 0 0 0
Neuraminidase3
  + + 0 0 0 0
Inclusions4
  C C N,C ? C ?


1Zoonotic paramyxoviruses.
2Hemolysin activity carried by F glycoprotein.
3Hemagglutination and neuraminidase activities carried by HN glycoprotein of respiroviruses and rubulaviruses; H glycoprotein of morbilliviruses lacks neuraminidase activity; G glycoprotein of other paramyxoviruses lacks both activities.
4C, cytoplasm; N, nucleus.
Parainfluenzaviruses and RSV produce acute respiratory diseases . morbilliviruses and mumps systemic disease = diversity! They also differ from Orthomyxoviruses genetically - non-segmented genome with little genetic variation


Morphology:
Glycoproteins - do not form such prominent spikes as on influenza virus:
· N – the nucleocapsid protein associates with genomic RNA (one molecule per hexamer) and protects the RNA from nuclease digestion
· P – the phosphoprotein binds to the N and L proteins and forms part of the RNA polymerase complex
· M – the matrix protein assembles between the envelope and the nucleocapsid core, it organizes and maintains virion structure
· F – the fusion protein projects from the envelope surface as a trimer, and mediates cell entry by inducing fusion between the viral envelope and the cell membrane by class I fusion.
· H/HN/G – the cell attachment proteins span the viral envelope and project from the surface as spikes. They bind to proteins on the surface of target cells to facilitate cell entry. Proteins are designated H (hemagglutinin) for morbilliviruses and henipaviruses as they possess haemagglutination activity, observed as an ability to cause red blood cells to clump. HN (Hemagglutinin-neuraminidase) attachment proteins occur in respiroviruses, rubulaviruses and avulaviruses. These possess both haemagglutination and neuraminidase activity which cleaves sialic acid on the cell surface, preventing viral particles from reattaching to previously infected cells. Attachment proteins with neither haemagglutination nor neuraminidase activity are designated G (glycoprotein). These occur in members of pneumovirinae.
· L – the large protein is the catalytic subunit of RNA-dependent RNA polymerase (RDRP)
· Accessory proteins – a mechanism known as RNA editing allows multiple proteins to be produced from the P gene. These are not essential for replication but may aid in survival in vitro or may be involved in regulating the switch from mRNA synthesis to antigenome synthesis.