Picornaviruses
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Picornaviruses |
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Enterovirus |
Picornaviruses are viruses that belong to the family Picornaviridae.
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 8.5kb 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 have not 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 untranslated 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 is this occurred in the nucleus.)
[edit] Structure of the Picornaviruses
The capsid is an arrangement of 60 protomers in a tightly packed Icosahedral structure. Each protomer consists of 4 polypeptides known as VP (viral protein)1, 2, 3 and 4. All of these VP polypeptides originate form 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 slip into 3 little triangles with a subunit on the corner.
Depending on the type and degree of dehydration the viral particle is around 27-30nm in diameter. The viral genome is around 2500nm in length so we can therefore conclude that it must be tightly packaged within the caspid along with substances such as sodium ions in order to cancel out the negative charges on the RNA caused by the phosphate groups.
[edit] Picornavirus replication
The viral particle binds to cell surface receptors. Once inside the cell the RNA uncoats and the genome is translated by host cell machinery in the cytoplasm. This is very rapid with the whole process of replication being competed 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 synthesised 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.
[edit] Types of Picornavirus
Contained within this family are many genera that contain important vertebrate/human pathogens, such as:
- Enteroviruses including Poliovirus
- Rhinovirus including Human rhinovirus A and others that are often the cause of the common cold
- Hepatovirus such as Hepatitis A virus
- Cardiovirus, there are currently only two species in this genus Encephalomyocarditis virus and Theilovirus
- Aphthovirus that are responsible for Foot-and-mouth disease virus O