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All About Rotavirus and It's Virology

BY: Preethi Venkateswaran | Category: Biotech-Research | Submitted: 2011-07-05 14:14:20
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Article Summary: "The name rotavirus comes from the Latin word 'rota' (means wheel), and it indeed looks like a wheel. Rotavirus, a non-enveloped virus with an 11-segment double stranded RNA genome, was first found in humans using electron microscopy in biopsies from children with acute gastroenteritis, before being first spotted in animals in 19.."


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The name rotavirus comes from the Latin word 'rota' (means wheel), and it indeed looks like a wheel. Rotavirus, a non-enveloped virus with an 11-segment double stranded RNA genome, was first found in humans using electron microscopy in biopsies from children with acute gastroenteritis, before being first spotted in animals in 1960's. Rotavirus belongs to the family of Reoviridae, a family of virus that can affect the gastrointestinal system. Rotavirus causes approximately 114 million cases of gastroenteritis per year of which 24 million cause clinic visits, thereby indicating the vicious nature of the virus. It severely affects children between the ages of 6 and 24 months. In the US, rotaviruses cause yearly epidemics of disease from late fall to early spring resulting in 20- 70 childhood deaths per; by the age of 5 almost every child is infected by the virus. Severity of the disease varies between the different locations. Clean sterile conditions and good water supplies are not limiting factors for the virus transmission, and do not prevent the spread of the disease.


The Virology

Rotavirus is icosahedral in shape and measures 70nm in diameter, as shown in Figure 2. There are seven serotypes of the virus namely A, B, C, D, E, F and G. Most common in humans are A, B and C where A causes diarrhea in US and is important from public standpoint. Groups B and C can cause gastroenteritis in adults. The virus has three protein shells, an inner capsid, an outer capsid and an outer core. These layers surround around 11 segments that code for 18,555 base pairs. Each helix is a gene numbered from 1 to 11 in the decreasing size. Each gene codes for a single protein except 9 and 11 which code for two. This might occur due to the mixed infection where more than one rotavirus occurs and there is re-assortment of gene segments producing mixed strain. There are both structural and non-structural proteins. Structural proteins are the viral proteins namely VP1, VP2, VP3, VP4, VP6 and VP7. Non-structural proteins, viz. NSP1, NSP2, NSP3, NSP4, NSP5 and NSP6, are produced in cells infected by rotavirus. Of these the most important proteins considered for vaccine development and research are VP6, NSP4, VP7 and VP4. VP7 is determined by serotype G. VP4, which is protein sensitive, is defined as P type. These genotypes are designated in brackets, for instance, P1A[8]. G serotypes numbered G1, G2 and so on. 14 G serotypes and 20 P serotypes have been identified so far. Fig.3 shows the pie distribution of rotavirus serotypes where 'others' are strains that were not identified. G and P serotypes differ according to their geographical locations. During implementation of new vaccines, the geographical locations of these strains must be taken into consideration.

Disease Mechanism and Diagnosis

The transmission happens via the oral fecal route. Naturally acquired rotavirus provides protection against the disease upon re-infection and the protection is greatest against the most severe outcomes. The disease mechanism is not thoroughly understood. The pathophysiology of the virus is being understood by using mouse models. Studies indicate that both humoral and cell-mediated immunity are important in the rotavirus infection and protection against the virus. The diagnosis of the disease can be done by stool analysis, enzyme immunoassays for rotavirus serum IgG and IgA antibodies that determine the rotavirus infections. Some other significant diagnostic tools are latex agglutination, electron microscopy and polyacryl amide gel electrophoresis.
Fig.4 shows a complete replication cycle. Here the virus attaches to the host cells via complex interactions of surface proteins, namely VP4 and VP7, using cellular receptors. Then endocytosis and uncoating occurs. Transcription of mRNA from all 11 genomic segments occurs and releases them into the cytoplasm where they are translated. Intracytoplasmic inclusion bodies termed as 'viroplasms' are formed. Within the viroplasms early morphogenesis takes place during which genome equivalents of viral RNA segments are packaged under strict control and then replicate to form the dsRNA genome. The detailed steps of this process are not clearly understood. Viral double layered particles (DLP) are released from viroplasms, and NSP4, incorporated into membranes of the rough endoplasmic reticulum acts as an intercellular receptor for DLPs for them to be processed to form the infectious,triple layered particles (TLPs) which are released by lysis.

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