1. Sadaf Batool Saadia Maqbool
Rotavirus
Sadaf Batool
Saadia Maqbool

2. Contents Introduction Viral Structure Genome Classification
Diagnosis and Symptoms
Replication
Transmission
Incubation period
Prevention and
Treatment

3. Rotavirus
Rotavirus makes a toxin called “NSP4 enterotoxin,” which alters the function of the intestines, causing increased fluid secretion and lactose intolerance.

4. 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
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

5. Genome Classifications
Viral Structure
&
Genome Classifications
Virus classification
Group:
Group III (dsRNA)
Order:
Unassigned
Family:
Reoviridae
Subfamily:
Sedoreovirinae
Genus:
Rotavirus

6. 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

7. 3 concentric icosahedral protein capsid layers
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

8. (The Ever-Changing Landscape of Rotavirus 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))

9. Types of Rotavirus

10. Groups D, E, and F rotaviruses have been found only in animals.
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.

12. Clinical Features & Diagnosis:

13. Diagnosis 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 
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.

14. Replication

15. Viral Replication
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.
It is able to do this because it brings its own polymerase into the cell as part of the viral particle.

16. Viral Replication Plus-strand RNAs direct protein synthesis
Also serve as templates for the synthesis of the SEGMENTED DOUBLE- STRANDED RNA (DSRNA) GENOME.

17. 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

18. Steps in Viral Replication
Receptor mediated endocytosis leading to formation of endosome
Viral RDRP (RNA Dependent RNA Polymerase) creates mRNA transcripts of the double- stranded viral genome
Viral genome is in the core of two layered protein shell termed as DLP (double layered particle)
Third layer is disrupted
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

19. Steps in Viral Replication
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
In this viroplasm RNA is replicated and the DLPs are assembled
The DLPs migrate to the endoplasmic reticulum where they obtain their third, outer layer
Progeny viruses are released from the cell by lysis

21. Transmission

22. UNICEF and World Health Organization
Transmission
"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

23. 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
Can be spread by contaminated:
Hands
Objects
Food
Water

24. Transmission
The feces of an infected person can contain more than 10 trillion infectious particles per gram
Only 10–100 of these are required to transmit infection to another person

25. Incubation Period

26. Incubation Period
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
During the rotavirus incubation period, a person is contagious and can pass the infection on to others.
Once the diarrhea has ended, a person is no longer contagious

27. Prevention

28. Prevention
Improved sanitation does not decrease the rate of hospitalization
Hence means of disease control is VACCINATION

29. Vaccination

30. Vaccination Rotarix by GlaxoSmithKline RotaTeq by Merck
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.
Rotarix by GlaxoSmithKline
RotaTeq by Merck

31. Treatment

32. Treatment Management of symptoms
Maintenance of dehydration is essential, children can die from severe dehydration
Oral rehydration
Hospitalization in severe cases where fluids are administered by intravenous drip or nasogastric tube

33. Thanks