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, Tuhokovirus 1, 2 and 3)
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)
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, Tuhokovirus 1, 2 and 3)
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)
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
Thegenomeconsists
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, 50nucleotidesin
length which acts as atranscriptionalpromoter.
A 5’ trailer sequence, 50-161 nucleotides
long
Intergenomic regions between eachgenewhich
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 (seeMononegavirales)
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.
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
mediatescell entryby
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 and henipaviruses as they possesshaemagglutinationactivity,
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 andneuraminidaseactivity
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 ofRNA-dependent
RNA polymerase(RDRP)
Accessory proteins–
a mechanism known as RNA editing (seeMononegavirales)
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
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