Paramyxovirus
Encyclopedia
Paramyxoviruses are virus
es of the Paramyxoviridae family of the Mononegavirales
order; they are negative-sense single-stranded RNA viruses responsible for a number of human and animal disease
s.
is non-segmented negative-sense RNA, 15-19 kilobases in length and contains 6-10 genes. Extracistronic (non-coding) regions include:
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:
, 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 (dog
s), phocine distemper virus
(seals), cetacean morbillivirus (dolphin
s and porpoise
s) 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.
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es of the Paramyxoviridae family of the Mononegavirales
Mononegavirales
The order Mononegavirales is the taxonomic home of numerous related viruses. Members of the order that are commonly known are, for instance, Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus. All of these viruses cause significant disease in...
order; they are negative-sense single-stranded RNA viruses responsible for a number of human and animal disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
s.
Genera
- Subfamily Paramyxovirinae
- Genus AvulavirusAvulavirusThe genus Avulavirus is one of seven genera in the family Paramyxoviridae and contains viruses that used to be classified in the genus Rubulavirus, but which infect birds and translate protein V from an edited RNA transcript...
(type species Newcastle disease virus) - Genus Ferlavirus (Fer-de-Lance virus)
- Genus HenipavirusHenipavirusHenipavirus is a genus of the family Paramyxoviridae, order Mononegavirales containing two established species, Hendra virus and Nipah virus. The henipaviruses are naturally harboured by Pteropid fruit bats , and some microbat species...
(type species Hendravirus; others include Nipahvirus) - Genus MorbillivirusMorbillivirusMorbillivirus is a genus belonging to the Paramyxoviridae family of viruses in the order Mononegavirales. Many members of the genus cause diseases, such as rinderpest and measles, and are highly infectious.- External links :* *...
(type species Measles virus; others include Rinderpest virus, Canine distemper virus, phocine distemper virusPhocine distemper virusPhocine distemper virus is a paramyxovirus of the genus morbillivirus that is pathogenic for pinniped species, particularly seals. Clinical signs include laboured breathing, fever and nervous symptoms....
, Peste des Petits Ruminants virus (PPR)) - Genus Respirovirus (type species Sendai virusSendai virusSendai virus , also known as murine parainfluenza virus type 1 or hemagglutinating virus of Japan , is a negative sense, single-stranded RNA virus of the Paramyxoviridae family, a group of viruses featuring, notably, the Morbillivirus and Rubulavirus genera...
; others include Human parainfluenza virusesHuman parainfluenza virusesHuman parainfluenza viruses are a group of four distinct serotypes of enveloped single-stranded RNA viruses belonging to the paramyxovirus family.Parainfluenza viruses can be detected via cell culture, immunofluorescent microscopy, and PCR....
1 and 3, as well some of the viruses of the common coldCommon coldThe common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
) - Genus RubulavirusRubulavirusRubulavirus is a genus of the Paramyxoviridae family of infectious viruses. The genus includes the mumps virus and parainfluenza type 2, 4a and 4b viruses.-External links:* http://www.biology-online.org/dictionary/Rubulavirus*...
(type species Mumps virusMumps virusMumps virus is the causative agent of mumps, a well-known common childhood disease characterised by swelling of the parotid glands and other epithelial tissues, causing high morbidity and in some cases more serious complications such as deafness...
; others include Human parainfluenza virusesHuman parainfluenza virusesHuman parainfluenza viruses are a group of four distinct serotypes of enveloped single-stranded RNA viruses belonging to the paramyxovirus family.Parainfluenza viruses can be detected via cell culture, immunofluorescent microscopy, and PCR....
2 and 4, Simian parainfluenza virus 5, Menangle virusMenangle virusMenangle virus is a virus that infects pigs, humans and bats.-History:Menangle virus was first identified in 1997 after a piggery in Menangle near Sydney, NSW, Australia experienced a high number of stillbirths and deformities during farrowing. Two workers at the piggery came down with an...
, Tioman virusTioman virusTioman virus is a paramyxovirus first isolated from the urine of island fruit bats on Tioman Island, Malaysia in 2000...
, Tuhokovirus 1, 2 and 3) - Genus TPMV-like viruses (type species Tupaia paramyxovirus)
- Genus Avulavirus
- Subfamily Pneumovirinae
- Genus Pneumovirus (type species Human respiratory syncytial virusHuman respiratory syncytial virusHuman respiratory syncytial virus is a virus that causes respiratory tract infections. It is the major cause of lower respiratory tract infections and hospital visits during infancy and childhood. A prophylactic medication exists for preterm birth infants and infants with a congenital heart...
, others include Bovine respiratory syncytial virus) - Genus MetapneumovirusMetapneumovirusHuman metapneumovirus is a negative single-stranded RNA virus of the family Paramyxoviridae and is closely related to the avian metapneumovirus subgroup C. It was isolated for the first time in 2001 in the Netherlands by using the RAP-PCR technique for identification of unknown viruses growing...
(type species Avian pneumovirusAvian pneumovirusAvian pneumovirus is a virus belonging to the Paramyxovirus family. It is a respiratory pathogen of turkeys and chickens. Turkeys are the most prone to developing the disease, especially when stocking density is high...
, Human metapneumovirus)
- Genus Pneumovirus (type species Human respiratory syncytial virus
- Unassigned viruses
- Atlantic salmon paramyxovirus
- Beilong virus
- J virus
- Menangle virusMenangle virusMenangle virus is a virus that infects pigs, humans and bats.-History:Menangle virus was first identified in 1997 after a piggery in Menangle near Sydney, NSW, Australia experienced a high number of stillbirths and deformities during farrowing. Two workers at the piggery came down with an...
- Mossman virus
- Nariva virus
- Pacific salmon paramyxovirus
- Salem virus
- Tailam virus
- Tioman virusTioman virusTioman virus is a paramyxovirus first isolated from the urine of island fruit bats on Tioman Island, Malaysia in 2000...
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 genomeGenome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
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 transcriptionTranscription (genetics)Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
al promoter. - A 5’ trailer sequence, 50-161 nucleotides long
- Intergenomic regions between each geneGeneA gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
, 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
Mononegavirales
The order Mononegavirales is the taxonomic home of numerous related viruses. Members of the order that are commonly known are, for instance, Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus. All of these viruses cause significant disease in...
) 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 entryViral entryViral entry is the earliest stage of infection in the viral life cycle, as the virus comes into contact with the host cell and introduces viral material into the cell. The major steps involved in viral entry are shown below. Despite the variation among viruses, the generalities are quite similar...
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 (hemagglutininHemagglutininInfluenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected...
) for morbilliviruses and henipaviruses as they possess haemagglutination activity, observed as an ability to cause red blood cells to clump in laboratory tests. HN (Hemagglutinin-neuraminidaseHemagglutinin-neuraminidaseHemagglutinin-neuraminidase refers to a single viral protein that has both hemagglutinin and neuraminidase activity. This is in contrast to the proteins found in influenza, where both functions exist but in two separate proteins....
) attachment proteins occur in respiroviruses, rubulaviruses and avulaviruses. These possess both haemagglutination and neuraminidaseNeuraminidaseNeuraminidase enzymes are glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread...
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 (glycoproteinGlycoproteinGlycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
). These occur in members of pneumovirinae. - L – the large protein is the catalytic subunit of RNA-dependent RNA polymeraseRNA-dependent RNA polymeraseRNA-dependent RNA polymerase , , or RNA replicase, is an enzyme that catalyzes the replication of RNA from an RNA template...
(RDRP) - Accessory proteins – a mechanism known as RNA editing (see MononegaviralesMononegaviralesThe order Mononegavirales is the taxonomic home of numerous related viruses. Members of the order that are commonly known are, for instance, Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus. All of these viruses cause significant disease in...
) 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 mumpsMumps
Mumps is a viral disease of the human species, caused by the mumps virus. Before the development of vaccination and the introduction of a vaccine, it was a common childhood disease worldwide...
, measles
Measles
Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
, which caused 745,000 deaths in 2001 and respiratory syncytial virus (RSV), which is the major cause of bronchiolitis
Bronchiolitis
Bronchiolitis is inflammation of the bronchioles, the smallest air passages of the lungs. It usually occurs in children less than two years of age and presents with coughing, wheezing, and shortness of breath. This inflammation is usually caused by viruses...
and pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
in infants and children.
The parainfluenza
Human parainfluenza viruses
Human parainfluenza viruses are a group of four distinct serotypes of enveloped single-stranded RNA viruses belonging to the paramyxovirus family.Parainfluenza viruses can be detected via cell culture, immunofluorescent microscopy, and PCR....
viruses are the second most common causes of respiratory tract disease in infants and children. They can cause pneumonia, bronchitis
Bronchitis
Acute bronchitis is an inflammation of the large bronchi in the lungs that is usually caused by viruses or bacteria and may last several days or weeks. Characteristic symptoms include cough, sputum production, and shortness of breath and wheezing related to the obstruction of the inflamed airways...
and croup
Croup
Croup is a respiratory condition that is usually triggered by an acute viral infection of the upper airway. The infection leads to swelling inside the throat, which interferes with normal breathing and produces the classical symptoms of a "barking" cough, stridor, and hoarseness...
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 (dog
Dog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...
s), phocine distemper virus
Phocine distemper virus
Phocine distemper virus is a paramyxovirus of the genus morbillivirus that is pathogenic for pinniped species, particularly seals. Clinical signs include laboured breathing, fever and nervous symptoms....
(seals), cetacean morbillivirus (dolphin
Dolphin
Dolphins are marine mammals that are closely related to whales and porpoises. There are almost forty species of dolphin in 17 genera. They vary in size from and , up to and . They are found worldwide, mostly in the shallower seas of the continental shelves, and are carnivores, mostly eating...
s and porpoise
Porpoise
Porpoises are small cetaceans of the family Phocoenidae; they are related to whales and dolphins. They are distinct from dolphins, although the word "porpoise" has been used to refer to any small dolphin, especially by sailors and fishermen...
s) Newcastle disease virus (birds), and rinderpest virus (cattle
Cattle
Cattle are the most common type of large domesticated ungulates. They are a prominent modern member of the subfamily Bovinae, are the most widespread species of the genus Bos, and are most commonly classified collectively as Bos primigenius...
). Some paramyxoviruses such as the henipaviruses are zoonotic
Zoonosis
A zoonosis or zoonoseis any infectious disease that can be transmitted from non-human animals to humans or from humans to non-human animals . In a study of 1415 pathogens known to affect humans, 61% were 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
Henipavirus
Henipavirus is a genus of the family Paramyxoviridae, order Mononegavirales containing two established species, Hendra virus and Nipah virus. The henipaviruses are naturally harboured by Pteropid fruit bats , and some microbat species...
have emerged in humans and livestock in Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...
and Southeast Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
. Both viruses are contagious
Contagious disease
A contagious disease is a subset category of infectious diseases , which are easily transmitted by physical contact with the person suffering the disease, or by their secretions or objects touched by them....
, highly virulent, and capable of infecting a number of mammalian species and causing potentially fatal disease. Due to the lack of a licensed vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
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.
New and emerging paramyxoviruses
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.Evolution
The evolution of this group 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.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