Paramyxoviridae

Paramyxovirus
Virus classification
Group:	Group V ((−)ssRNA)
Order:	Mononegavirales
Family:	Paramyxoviridae
Genera
Subfamily: Paramyxovirinae Aquaparamyxovirus Avulavirus Ferlavirus Henipavirus Morbillivirus Respirovirus Rubulavirus TPMV-like viruses Subfamily: Pneumovirinae Metapneumovirus Pneumovirus

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 Aquaparamyxovirus ( type species Atlantic salmon paramyxovirus: others include Pacific salmon paramyxovirus)
  • Genus Avulavirus (type species Newcastle disease virus)
  • Genus Ferlavirus (Fer-de-Lance 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, Ovine rinderpest)
  • 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 Achimota virus 1 and 2, Human parainfluenza viruses 2 and 4, Simian parainfluenza virus 5, Menangle virus, Tioman virus, Tuhokovirus 1, 2 and 3)
  • Genus TPMV-like viruses (type species Tupaia paramyxovirus: other species Mossman virus, Nariva virus and Salem virus)
  • Species Beilong virus

• 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
  • J virus
  • Sunshine virus
  • Tailam virus

Notes

The Beilong virus is now known to be a member of the subfamily Paramyxovirinae. It was isolated from rat kidney and its pathogenic potential is unknown. J virus is very similar to Beilong virus and probably belongs in the same genus. Both have features that differ from the other genera in this family. Tailam virus may also belong in this genus.

The relations between the salmon paramyxoviruses and the others have been poorly studied to date and their relationship to the other members of this genus is not currently known.

Sunshine virus was isolated from pythons in Australia. It appears to be unrelated to other known members of this taxon.

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 is non-segmented negative-sense RNA, 15–19 kilobases in length and contains 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 is a result of structure of the genome. After each gene is transcribed, the RNA-Dependent RNA polymerase pauses to release the new mRNA when it encounters an intergenic sequence. When the RNA polymerase is paused, there is a chance that it will dissociate from the RNA genome. If it dissociates, it must reenter the genome at the leader sequence, rather than continuing to transcribe the length of the genome. The result is that the further downstream genes are from the leader sequence, the less they will be transcribed by RNA polymerase.

Evidence for a single promoter model was verified when viruses were exposed to UV light. UV radiation can cause dimerization of RNA, which prevents transcription by RNA polymerase. If the viral genome follows a multiple promoter model, the level inhibition of transcription should correlate with the length of the RNA gene. However, the genome was best described by a single promoter model. When paramyxovirus genome was exposed to UV light, the level of inhibition of transcription was proportional to the distance from the leader sequence. That is, the further the gene is from the leader sequence, the greater the chance of RNA dimerization inhibiting RNA polymerase.

The virus takes advantage of the single promoter model by having its genes arranged in relative order of protein needed for successful infection. For example, nucleocapsid protein, N, is needed in greater amounts than RNA polymerase, L.

Many Paramyxovirus genomes follow the Rule of Six. The total length of the genome is almost always a multiple of six. This is probably due to the advantage of having all RNA bound by N protein (since N binds hexamers of RNA). If RNA is left exposed, the virus does not replicate efficiently. Members of the sub-family Pneumovirinae do not follow this rule

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 proteins on the surface of target cells to facilitate cell entry. Proteins are designated H (hemagglutinin) for morbilliviruses as they possess haemagglutination activity, observed as an ability to cause red blood cells to clump in laboratory tests. 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 and Henipaviruses.
• 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

Phylogenetic tree based on the N protein sequences of selected paramyxoviruses
Virus names are as follows: Avian paramyxovirus 6 (APMV6); Atlantic salmon paramyxovirus; Beilong virus (BeiPV) ; Bovine parainfluenza virus 3 (bPIV3); Canine distemper virus (CDV); Cedar virus (CedPV); Fer-de-lance virus (FdlPV) ; Hendra virus (HeV); Human parainfluenza virus 2 (hPIV2); Human parainfluenza virus 3 (hPIV3) ; Human parainfluenza virus 4a (hPIV4a) ; Human parainfluenza virus 4b (hPIV4b); J virus (JPV); Menangle virus (MenPV); Measles virus (MeV); Mossman virus (MosPV); Mapeura virus (MprPV); Mumps virus (MuV); Newcastle disease virus (NDV); Nipah virus, Bangladesh strain (NiV-B); Nipah virus, Malaysian strain (NiV-M); Parainfluenza virus 5 (PIV5); Peste-des-petits-ruminants (PPRV); Porcine rubulavirus (PorPV); Rinderpest virus (RPV); Salem virus (SalPV); Sendai virus (SeV); Simian virus 41 (SV41); Tioman virus (TioPV); Tupaia paramyxovirus (TupPV).

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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. Though it was discovered in 2001 it was proven to be circulating in the population for at least 50 years and that by the age of five most children have already been exposed to it.

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.

Diversity and evolution

The family Paramyxoviridae is composed of a diverse group of viruses and is divided into two subfamilies, Paramyxovirinae and Pneumovirinae. There are currently 40 virus species classified within the Paramyxovirinae subfamily, but several remain unclassified at the genus level. In the past few decades, paramyxoviruses have been discovered from terrestrial, volant and aquatic animals, demonstrating a vast host range and great viral genetic diversity. As molecular technology advances and viral surveillance programs are implemented, the discovery of new viruses in this group is increasing.

The evolution of paramyxoviruses is still debated. Using the pneumovirus as an outgroup, the Paramyxovirinae can be divided into two clades: one with the avulaviruses and rubulaviruses and the other with the respiroviruses, the henipaviruses and the morbilliviruses. Within the second clade the respiroviruses appear to be the basal group. The respirovirus-henipavirus-morbillivirus may be basal to the avulavirus-rubulavirus clade.

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 Genomes Viral Bioinformatics Resource Center
• Viralzone: Paramyxoviridae
• Virus Pathogen Database and Analysis Resource (ViPR): Paramyxoviridae