Paramyxovirus

Paramyxoviruses (from Greek para-, beyond, -myxo-, mucus or slime, plus virus, from Latin poison, slime) are viruses of the Paramyxoviridae family of the Mononegavirales order; they are negative-sense single-stranded RNA viruses responsible for a number of human and animal diseases.

Genera

• Subfamily Paramyxovirinae
  • Genus Avulavirus (type species Newcastle disease virus)
  • Genus Henipavirus (type species Hendravirus; others include Nipahvirus)
  • Genus Morbillivirus (type species Measles virus; others include Rinderpest virus, Canine distemper virus, phocine distemper virus, Peste des Petits Ruminants virus (PPR))
  • Genus Respirovirus (type species Sendai virus; others include Human parainfluenza viruses 1 and 3, as well some of the viruses of the common cold)
  • Genus Rubulavirus (type species Mumps virus; others include Human parainfluenza viruses 2 and 4, Simian parainfluenza virus 5, Menangle virus, Tioman virus)
  • Genus TPMV-like viruses (type species Tupaia paramyxovirus)
• Subfamily Pneumovirinae
  • Genus Pneumovirus (type species Human respiratory syncytial virus, others include Bovine respiratory syncytial virus)
  • Genus Metapneumovirus (type species Avian pneumovirus, Human metapneumovirus)
• Unassigned viruses
  • Fer-de-Lance virus
  • Nariva virus
  • Tupaia paramyxovirus
  • Salem virus
  • J virus
  • Mossman virus
  • Beilong virus

Physical structure

Virions are enveloped and can be spherical, filamentous or pleomorphic. Fusion proteins and attachment proteins appear as spikes on the virion surface. Matrix proteins inside the envelope stabilise virus structure. The nucleocapsid core is composed of the genomic RNA, nucleocapsid proteins, phosphoproteins and polymerase proteins.

Genome structure

The genome consists of a single NOT segment negative-sense RNA, 15-19 kilobases in length and containing 6-10 genes. Extracistronic (non-coding) regions include:

• A 3’ leader sequence, 50 nucleotides in length which acts as a transcriptional promoter.
• A 5’ trailer sequence, 50-161 nucleotides long
• Intergenomic regions between each gene which are three nucleotides long for morbillivirus, respirovirus and henipavirus, variable length (1-56 nucleotides) for rubulavirus and pneumovirinae.

Each gene contains transcription start/stop signals at the beginning and end which are transcribed as part of the gene.

Gene sequence within the genome is conserved across the family due to a phenomenon known as transcriptional polarity (see Mononegavirales) in which genes closest to the 3’ end of the genome are transcribed in greater abundance than those towards the 5’ end. This mechanism acts as a form of transcriptional regulation.

The gene sequence is:

• Nucleocapsid – Phosphoprotein – Matrix – Fusion – Attachment – Large (polymerase)

Proteins

• 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. One of the defining characteristics of members of the paramyxoviridae family is the requirement for a neutral pH for fusogenic activity.
• H/HN/G – the cell attachment proteins span the viral envelope and project from the surface as spikes. They bind to sialic acid on the cell surface and facilitate cell entry. Note that the receptor for measles virus is unknown. Proteins are designated H for morbilliviruses and henipaviruses as they possess haemagglutination activity, observed as an ability to cause red blood cells to clump. HN 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 (see Mononegavirales) 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.

Pathogenic paramyxoviruses

A number of important human diseases are caused by paramyxoviruses. These include mumps, measles, which caused 745,000 deaths in 2001 and respiratory syncytial virus (RSV) which is the major cause of bronchiolitis and pneumonia in infants and children.

The parainfluenza viruses are the second most common causes of respiratory tract disease in infants and children. They can cause pneumonia, bronchitis and croup in children and the elderly.

Human metapneumovirus, initially described in about 2001, is also implicated in bronchitis, especially in children.

Paramyxoviruses are also responsible for a range of diseases in other animal species, for example canine distemper virus (dogs), phocine distemper virus (seals), cetacean morbillivirus (dolphins and porpoises) Newcastle disease virus (birds) and rinderpest virus (cattle). Some paramyxoviruses such as the henipaviruses are zoonotic pathogens, occurring naturally in an animal host, but also able to infect humans.

Hendra virus (HeV) and Nipah virus (NiV) in the genus Henipavirus have emerged in humans and livestock in Australia and Southeast Asia. Both viruses are contagious, highly virulent, and capable of infecting a number of mammalian species and causing potentially fatal disease. Due to the lack of a licensed vaccine or antiviral therapies, HeV and NiV are designated as biosafety level (BSL) 4 agents. The genomic structure of both viruses is that of a typical paramyxovirus.^[1]

See also

• Animal viruses
• Virology
• Henipavirus

External links

• Paramyxoviruses (1998) — morphology, genome, replication, pathogenesis (special access required)
• Hendra virus has a growing family tree (2001) CSIRO Paramyxovirus press release
• Animal viruses
• Paramyxoviridae GenomesViral Bioinformatics Resource Center
• Viralzone: Paramyxoviridae

References