Sadaf Batool

Saadia Maqbool

Rotavirus

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))

Types of Rotavirus

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.

Clinical Features & Diagnosis:

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

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.

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

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

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

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

Incubation Period

Prevention

Improved sanitation does not decrease the rate of hospitalization

Prevention

Hence means of disease control is VACCINATION

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

Treatment

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

Thanks