Thursday, January 15, 2009 1:16 PM
Class IIIClass III viruses are double stranded RNA viruses that regulates replication, transcription, and translation separately, and has segmented genome. All replication activity is in cytoplasm, not nucleus.
An example of a virus from class III is Reoviridae.
Reoviridae
Reoviridae is a family of viruses that can affect the gastrointestinal system (such as Rotavirus) and respiratory tract.
Viruses in the family Reoviridae have genomes consisting of segmented, double-stranded RNA (dsRNA).
Reovirus infection occurs often in humans, but most cases are mild or subclinical.
The virus can be readily detected in feces, and may also be recovered from pharyngeal or nasal secretions, urine, cerebrospinal fluid, and blood.
Despite the ease of finding Reovirus in clinical specimens, their role in human disease or treatment is still uncertain.
Twelve genera of Reoviridae exist and are divided based on the presence of a "turret" protein on the inner capsid.
Turreted
- Genus Aquareovirus: type species Aquareovirus A
- Genus Cypovirus: type species Cypovirus 1 (CPV 1)
- Genus Fijivirus: type species Fiji disease virus
- Genus Idnoreovirus: type species Idnoreovirus 1
- Genus Mycoreovirus: type species Mycoreovirus 1
- Genus Orthoreovirus: type species Mammalian orthoreovirus
- Genus Oryzavirus: type species Rice ragged stunt virus
Nonturreted
- Genus Coltivirus: type species Colorado tick fever virus (CTFV)
- Genus Orbivirus: type species Bluetongue virus
- Genus Phytoreovirus: type species Rice dwarf virus
- Genus Rotavirus: type species Rotavirus A - a common cause of primarily early childhood diarrhea
- Genus Seadornavirus
Virology
Genome
The genome of rotavirus consists of 11 unique double helix molecules of RNA which are 18,555 nucleoside base-pairs in total.
Each helix, or segment, is a gene, numbered 1 to 11 by decreasing size. Each gene codes for one protein, except genes 9 and 11, which each code for two.
The RNA is surrounded by a three-layered icosahedral protein capsid. Viral particles are up to 76.5 nm in diameter and are not enveloped.
Replication
A simplified drawing of the rotavirus replication cycle
Rotavirus infects enterocytes of the villi of the small intestine, leading to structural and functional changes of the epithelium.
The triple protein coats make them resistant to the acidic pH of the stomach and the digestive enzymes in the gut.
The virus enter cells by receptor mediated endocytosis and form a vesicle known as an endosome.
Proteins in the third layer (VP7 and the VP4 spike) disrupt the membrane of the endosome, creating a difference in the calcium concentration.
This causes the breakdown of VP7 trimers into single protein subunits, leaving the VP2 and VP6 protein coats around the viral dsRNA, forming a double-layered particle (DLP).
The eleven dsRNA strands remain within the protection of the two protein shells and the viral RNA-dependent RNA polymerase creates mRNA transcripts of the double-stranded viral genome.
By remaining in the core, the viral RNA evades innate host immune responses called RNA interference that are triggered by the presence of double-stranded RNA.
During the infection, rotavirus produces mRNA for both protein biosynthesis and gene replication.
Most of the rotavirus proteins accumulate in viroplasm, where the RNA is replicated and the DLPs are assembled.
Viroplasm is formed around the cell nucleus as early as two hours after virus infection, and consists of viral factories thought to be made by two viral nonstructural proteins: NSP5 and NSP2.
Inhibition of NSP5 by RNA interference results in a sharp decrease in rotavirus replication.
The DLPs migrate to the endoplasmic reticulum where they obtain their third, outer layer (formed by VP7 and VP4).
The progeny viruses are released from the cell by lysis.
Pathogenesis
Rotavirus gastroenteritis is a mild to severe disease characterised by vomiting, watery diarrhoea, and low-grade fever.
Once a child is infected by the virus, there is an incubation period of about two days before symptoms appear.
Symptoms often start with vomiting followed by four to eight days of profuse diarrhoea.
Dehydration is more common in rotavirus infection than in most of those caused by bacterial pathogens, and is the most common cause of death related to rotavirus infection.
Clinical Features
Acute
first infection usually produces symptoms,
symptomatic infection rates are highest in children under two years of age
severe symptoms tend to occur in children six months to two years of age, the elderly, and those with compromised or absent immune system functions
Chronic
subsequent infections are typically asymptomatic,as immune system provides protection Infection in newborn children, although common, is often associated with mild or asymptomatic
disease
• Due to immunity acquired in childhood, most adults are not susceptible to rotavirus; gastroenteritis in adults usually has a cause other than rotavirus, but asymptomatic infections in adults may maintain the transmission of infection in the community.
Symptomatic reinfections are often due to a different rotavirus A serotype.
Lab Diagnosis
Specific diagnosis of infection with rotavirus A is made by identification of the virus in the patient's stool by enzyme immunoassay.
There are several licensed test kits on the market which are sensitive, specific and detect all serotypes of rotavirus A.
Other methods, electron microscopy and polyacrylamide gel electrophoresis, are used in research laboratories.
Reverse transcription-polymerase chain reaction (RT-PCR) can detect and identify all species and serotypes of human rotavirus.
Treatment and prognosis
• nonspecific
• involves management of symptoms
• maintenance of hydration.
• oral rehydration with plain water, water plus salts, or water plus salts and sugar
• Serious infections - hospitalisation where fluids are given by intravenous drip or nasogastric tube and child's electrolytes and blood sugar are monitored
Done by: Alyssa Huang