Transcript Group A
Sadaf Batool Saadia Maqbool Introduction Viral Structure Genome Classification Diagnosis and Symptoms Replication Transmission Incubation period Prevention and Treatment Rotavirus 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 Spreads mostly in winter & spring Causes severe kind of diarrhea Poor hygiene conditions worsen the condition Most severe diarrhea cases “rotavirus gastroenteritis ” Good hygiene Virus remain stable & infective in environment 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 Prevents Cures Under developed Countries at higher risk??? Children till the age of 3 Centers for Disease Control and Prevention say: 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 Viral Structure & Genome Classifications Virus classification Group: Group III (dsRNA) Order: Unassigned Family: Reoviridae Subfamily: Sedoreovirinae Genus: Rotavirus 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 It forms 60 spikes of envelope Inner capsid consists of VP6 protein. VP 5 VP 8 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 VP3 Abundant most core protein (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)) Group A: Found world wide as a cause of – Group C: gastroenteritis in humans as well as • This group also affects children animals. • However occurrence of people It accounts for more than half of the acquiring this infection is very rare. hospitalization Groups cases from severe D, E, and F rotaviruses haveoutbreaks been were reported in • First diarrhea in infants and children, world found only in animals. Japan and England. wide. In temperate regions, the infection is caused in winters – Novel types: In tropics, it may cause infection • These have been the only 3 groups of 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. 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 Clinical Features & Diagnosis: Symptoms Diagnosis The symptoms usually The incubation period of this 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 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. 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. Plus-strand RNAs direct protein synthesis Also serve as templates for the synthesis of the SEGMENTED DOUBLESTRANDED RNA (DSRNA) GENOME. 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 1. Receptor mediated endocytosis leading to formation of endosome 3. Third layer is disrupted 4. 2. Viral RDRP (RNA Dependent RNA Polymerase) creates mRNA transcripts of the doublestranded viral genome 3. Viral genome is in the core of two layered protein shell termed as DLP (double layered particle) By remaining in the core, the viral RNA evades innate host immune responses called RNA interference that are triggered by the presence of doublestranded RNA 6. 7. Viroplasm is formed 8. around the cell nucleus as early as two hours after virus infection, and consists of viral factories thought to be made by two viral 9. 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 "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 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 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 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 Improved sanitation does not decrease the rate of hospitalization 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. • Rotarix by GlaxoSmithKline • RotaTeq by Merck 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