Friday, September 18, 2009

Picornavirus


A Picornavirus is a virus belonging to the family Picornaviridae. Picornaviruses are non-enveloped, positive-stranded RNA viruses with an icosahedral capsid. The genome RNA is unusual because it has a protein on the 5' end that is used as a primer for transcription by RNA polymerase. The name is derived from pico meaning small, and RNA referring to the ribonucleic acid genome, so "picornavirus" literally means small RNA virus.
Picornaviruses are separated into nine distinct genera and include many important pathogens of humans and animals.[1] The diseases they cause are varied, ranging from acute "common-cold"-like illnesses, to poliomyelitis, to chronic infections in livestock. Two main categories are enteroviruses and rhinoviruses.
Classification
Picornaviruses are classed under Baltimore's viral classification system as group IV viruses as they contain a single stranded, positive sense RNA genome of between 7.2 and 9.0 kb in length. Like most positive sense RNA genomes, the genetic material alone is infectious; although substantially less virulent than if contained within the viral particle, the RNA can have increased infectivity when transfected into cells. The genome itself is the same sense as mammalian mRNA, being read 5’ to 3’. Unlike mammalian mRNA Picornaviruses do not have a 5’ CAP but a virally encoded protein known as VPg, however like mammalian mRNA the genome does have a poly A tail at the 3’ end. There is an un-translated region (UTR) at both ends of the Picornavirus genome. The 5’ UTR is longer, being around 600-1200 BP in length, compared to that of the 3’ UTR, which is around 50-100bp. It is thought that the 5’ UTR is important in translation and the 3’ in negative strand synthesis; however the 5’ end may also have a role to play in virulence of the virus. The rest of the genome encodes structural proteins at the 5’ end and non-structural proteins at the 3’ end in a single polyprotein. Experimental data from single step growth-curve-like experiments have allowed scientists to look at the replication of the picornaviruses in great detail. The whole of replication occurs within the host cell cytoplasm and infection can even happen in cells that do not contain a nucleus (known as enucleated cells) and those treated with actinomycin D (this antibiotic would inhibit viral replication if this occurred in the nucleus.)
Picornaviruses are separated into nine distinct genera. Contained within the picornavirus family are many organisms of importance as vertebrate and human pathogens, shown in the table below.
Picornavirus Genera, Species and Serotypes
Species (* signifies type species)
two types: bovine enterovirus (BEV) 1 and BEV-2
Human enterovirus A
21 types including some coxsackie A viruses and enteroviruses
Human enterovirus B
57 types including enteroviruses, coxsackie B viruses, echoviruses, and swine vesicular disease virus
Human enterovirus C
14 types including some coxsackie A viruses and enteroviruses
Human enterovirus D
three types: EV-68, EV-70, EV-94
three types: poliovirus (PV) 1, PV-2 and PV-3
one type: porcine enterovirus (PEV) 8
Porcine enterovirus B
two types: PEV-9 and PEV-10
one type: simian enterovirus (SEV) A1
Human rhinovirus A *
74 serotypes
Human rhinovirus B
25 serotypes
Human rhinovirus C
7 serotypes
Hepatovirus (also classed as Heparnavirus)
Hepatitis A virus *
one serotype: Hepatitis A virus (HAV)
one type: avian encephalomyelitis virus (AEV)
one serotype: encephalomyocarditis virus (EMCV). Note: Columbia SK virus, Maus Elberfeld virus and Mengovirus are strains of EMCV.
five types: Theiler's murine encephalomyellitis virus (TMEV), Vilyuisk human encephalomyelitis virus (VHEV), Theiler-like virus (TLV) of rats, Saffold virus (SAFV) 1 and SAFV-2
seven serotypes: O, A, C, Southern African Territories (SAT) 1, SAT 2, SAT 3 and Asia 1
Equine rhinitis A virus
single serotype: equine rhinitis A virus (ERAV)
Human parechovirus *
six types: Human parechovirus (HPeV) 1, HPeV-2, HPeV-3, HPeV-4, HPeV-5, HPeV-6
Possibly three types have been described
Equine rhinitis B virus *
Three types: equine rhinitis B virus (ERBV) 1, ERBV-2, ERBV-3
single serotype: Aichi virus (AiV)
Single serotype: bovine kobuvirus (BKV)
11 serotypes: porcine teschovirus (PTV) 1 to PTV-11
Sources
Enteroviruses infect the enteric tract as it is visible from its name. On the other hand, rhinoviruses infect primarily the nose and the throat. Enteroviruses replicate at 37°C, whereas Rhinoviruses grow better at 33°C, as this is the lower temperature of the nose. Enteroviruses are stable under acid conditions and thus they are able to survive exposure to gastric acid. In contrast, Rhinoviruses are acid-labile and that is the reason why Rhinoviruses are restricted to the nose and throat.
Plant picornaviruses
The plant picornaviruses have a number of properties that are distinct from the animal viruses. They have been classified into a superfamily Secoviridae containing the families Comoviridae (genera Comovirus, Fabavirus and Nepovirus), Sequiviridae (genera Sequivirus and Waikavirus) and a number of unassigned genera (Cheravirus, Sadwavirus and Torradovirus (type species Tomato torrado virus)).[3]
Virology
Structure
The capsid is an arrangement of 60 protomers in a tightly packed Icosahedral structure. Each protometer consists of 4 polypeptides known as VP (viral protein)1, 2, 3 and 4. VP2 and VP4 polypeptides originate from one protomer known as VP0 that is cleaved to give the different capsid components. The Icosahedral is said to have a triangulation number of 3, this means that in the icosahedral structure each of the 60 triangles that make up the capsid are split into 3 little triangles with a subunit on the corner. Depending on the type and degree of dehydration the viral particle is around 27-30 nm in diameter. The viral genome is around 2500 nm in length so we can therefore conclude that it must be tightly packaged within the capsid along with substances such as sodium ions in order to cancel out the negative charges on the RNA caused by the phosphate groups.
Replication
The viral particle binds to cell surface receptors. This causes a conformational change in the viral capsid proteins, and myristic acids are released. These acids form a pore in the cell membrane through which RNA is injected[1]. Once inside the cell, the RNA un-coats and the (+) strand RNA genome is replicated through a double-stranded RNA intermediate that is formed using viral RDRP (RNA-Dependent RNA polymerase). Translation by host cell ribosomes is not initiated by a 5' G cap as usual, but rather is initiated by an IRES (Internal Ribosome Entry Site). The viral lifecycle is very rapid with the whole process of replication being completed on average within 8 hours. However as little as 30 minutes after initial infection, cell protein synthesis declines to almost zero output – essentially the macromolecular synthesis of cell proteins is “shut off”. Over the next 1–2 hours there is a loss of margination of chromatin and homogeneity in the nucleus, before the viral proteins start to be synthesized and a vacuole appears in the cytoplasm close to the nucleus that gradually starts to spread as the time after infection reaches around 3 hours. After this time the cell plasma membrane becomes permeable, at 4–6 hours the virus particles assemble, and can sometimes be seen in the cytoplasm. At around 8 hours the cell is effectively dead and lyses to release the viral particles.
History
In 1897, foot-and-mouth disease virus (FMDV), the first animal virus, was discovered. FMDV is the prototypic member of the Aphthovirus genus in the Picornaviridae family. [2] The plaque assay was developed using poliovirus. Both RNA dependent RNA polymerase and polyprotein synthesis were discovered by studying poliovirus infected cells.


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