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IntroductionViral Structure Genome ClassificationDiagnosis and Symptoms
Contents
ReplicationTransmission
Incubation periodPrevention and
Treatment
RotavirusRotavirus makes a toxin called
“NSP4 enterotoxin,” which alters the function of the
intestines, causing increased fluid secretion and lactose
intolerance.
Rota is Greek word for Wheel
Causes severe kind of diarrhea
Most severe diarrhea cases “rotavirus gastroenteritis ”
Virus remain stable & infective in environment
Centers for Disease Control and Prevention say: Children till the age of 3
most susceptible and most frequently infected group
All children would have acquired it by the age of 5, atleast once
Disease deadly if acquired in first 24 hours of birth
Intensity decreases : in second infection in adults
Spreads mostly in winter & spring
Poor hygiene conditions worsen the condition
Good hygiene Prevents Cures
Under developed Countries at higher risk??? Poor hygiene Inappropriate health care Malnutrition
Highly contagious virus
Infection may spread (fecal-oral route of transmission) From children to children From children to adults
Virus classification
Group: Group III (dsRNA)
Order: Unassigned
Family: Reoviridae
Subfamily: Sedoreovirinae
Genus: Rotavirus
Viral Structure &
Genome Classifications
Belongs to family Reoviridae contain segmented double-stranded RNA
as genome (18522 bp long app)
Intact virus particles resemble a wheel, with short spikes and a well-defined rim.
Size ranges upto 100 nm
Non-enveloped viruses
Genome of 11 double-stranded RNA segments which encode: Six structural (VP1–VP6) Six non-structural (NSP1-NSP6) proteins
Expressed by viral genome but not incorporated in mature viriod
Play important role in virus replication morphogenesis and Pathogenesis
Segment 11 encoding both NSP5 and NSP6 from two overlapping open reading frames
A specific intimate protein-RNA interaction leads to bending & fitting of 11 segments in viral core.
3 concentric icosahedral protein capsid layers Outer capsid consists of 2 proteins
VP 7 glycoprotein VP 4 gp
In order to increase viral infectivity, It cleaves into VP 5 VP 8
It forms 60 spikes of envelope Inner capsid consists of VP6 protein.
It is used for the determination of groups and sub-groups owing to protein specificity
Connected to enterotoxin NSP4. Core consists of:
VP 1 VP2
Abundant most core protein VP3
(The Ever-Changing Landscape ofRotavirus Serotypes
At present, 5 rotavirus serotypes (G1, G2, G3, G4, G9) are the predominant circulating strains, accounting for
approximately 95% of strains worldwide(The Pediatric Infectious Disease
Journal:Volume 28(3) Supplement March 2009pp S60-S62))
The most commonly known Serogroups of rotavirus.The species are differentiated on the basis of antigenecity of the capsid protein VP6. These are called group A-G rotavirus.
Group A: Found world wide as a cause of
gastroenteritis in humans as well as animals.
It accounts for more than half of the hospitalization cases from severe diarrhea in infants and children, world wide.
In temperate regions, the infection is caused in winters
In tropics, it may cause infection through out the year
– Group B:• It is commonly termed as adult
diarrhea rotavirus or ADRV Primary affectees are adults However, it has been major
epidemic of diarrhea for all ages in China.
– Group C:• This group also affects children• However occurrence of people
acquiring this infection is very rare.• First outbreaks were reported in Japan
and England.
– Novel types:• These have been the only 3 groups of
rota viruses infecting human lately, however recently 2 new rotaviruses (not classified in any of A-G) have been reported to have caused disease in human. These are :
ADRV-N: Reported in China B219 : Reported in Bangladesh
Groups D, E, and F rotaviruses have been found only in animals.
Diagnosis
The incubation period of this virus is 2 days, after which it begins to show symptoms. however this virus is found excessively in stool before and after the infection. Antigen test: the presence
of specific antigen in stool gives positive result, thus giving away the presence of virus.
ELISA: this test further determines the specific strain of virus.
RTPCR: this test is also performed but not excessively.
Symptoms
The symptoms usually persist from 3-8/9 days. Frequent, watery diarrhea Vomiting Fever Stomach cramps Nausea Dehydration
Thirst, irritability, restlessness, lethargy, sunken eyes, a dry mouth and tongue, cool dry skin, absence of tears while crying, fewer trips to the bathroom to urinate, and (in infants) a dry diaper for several hours.
Cough and runny nose in children
Very few or no symptoms in adults
Only one of the rotavirus segments, the minus strand, is used as a template for making messenger RNAs
Unlike DNA viruses, it conducts its lifecycle in the cytoplasm, NEVER MOVING INTO THE NUCLEUS.
Viral ReplicationIt is able to do this
because it brings its own polymerase into the cell as part of the viral particle.
Plus-strand RNAs direct protein synthesis
Also serve as templates for the synthesis of the SEGMENTED DOUBLE-STRANDED RNA (DSRNA) GENOME.
Viral Replication
Replication mainly in GUT (Intestinal epithelium)
Infection of enterocytes (cells of small intestine) in villi of small intestine
Leading to structural and functional changes of epithelium
Resistant to digestive enzymes and pH of stomach due to triple protein coat
Viral Replication
1. Receptor mediated endocytosis leading to formation of endosome
2. Viral RDRP (RNA Dependent RNA Polymerase) creates mRNA transcripts of the double-stranded viral genome
3. Viral genome is in the core of two layered protein shell termed as DLP (double layered particle)
Steps in Viral Replication3. Third layer is disrupted
4. 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
Steps in Viral Replication6. 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
7. In this viroplasm RNA is replicated and the DLPs are assembled
8. The DLPs migrate to the endoplasmic reticulum where they obtain their third, outer layer
9. Progeny viruses are released from the cell by lysis
"Rotavirus is estimated to cause about 40 per cent of all hospital admissions due to diarrhea
among children under five years of age worldwide—leading to some 100 million
episodes of acute diarrhea each year that result in 350,000 to 600,000 child deaths.“
UNICEF and World Health Organization
Transmission
Human–human Oral-fecal route
Virus is shed into the person’s stool
If any one gets in contact with the virus and “ingests” via mouth will be infected
Transmission
Can be spread by contaminated:
HandsObjectsFood Water
The feces of an infected person can contain more than 10 trillion infectious particles per gram
Transmission
Only 10–100 of these are required to transmit infection to another person
Time between when a person becomes infected and when symptoms appear
For rotavirus, the incubation period lasts approximately 2 to 4 days
When a person becomes infected with rotavirus, the virus begins to multiply within the small intestine. After approximately two days, symptoms of a rotavirus infection can appear
Incubation Period
Improved sanitation does not decrease the rate of hospitalization
Prevention
Hence means of disease control is VACCINATION
In 2006, two vaccines against Rotavirus A infection were shown to be safe and effective in children
Both take oral route and contain live attenuated virus
WHO now recommends that rotavirus vaccine be included in all national immunization programs
Additional rotavirus vaccines are under development.
Vaccination• Rotarix by
GlaxoSmithKline• RotaTeq by Merck
Management of symptoms
Maintenance of dehydration is essential, children can die from severe dehydration
Treatment
Oral rehydration
Hospitalization in severe cases where fluids are administered by intravenous drip or nasogastric tube