p resented by g roup 7 pcl2 rotavirus. g roup 7 members : nsabimana venuste 12113664 nyaziyose...
TRANSCRIPT
PRESENTED BY GROUP 7 PCL2
Rotavirus
GROUP 7 MEMBERS: NSABIMANA Venuste 12113664NYAZIYOSE Ignace 12113538 NZABONIMPA Clarisse 12112932 NZIYOMAZE Elie 12114015 NZAHUMUNYURWA Donat 12113484 RUGIRA Vive 12113869 RUKAMBA Jean de Dieu 12113905 SHABELI Philippe 12113979 SHEMA Origène 12114300 SIMBI Credo Sylvie 12113714 TSEMO Tagne Sandrine 213003054 TUYISENGE Elius 12113225
ROTAVIRUSROTAVIRUSFamily Reoviridae
Genus Rotavirus
INTRODUCTION
Diarrheal disease has been recognized in humans since antiquity.
Until the early 1970s, a bacterial, viral, or parasitic etiology of diarrheal disease in children could be detected in fewer than 30% of cases
In 1973, Bishop and colleagues observed a virus particle in the intestinal tissue of children with diarrhea by using electron micrography.
This virus was subsequently called “rotavirus” because of its similarity in appearance to a wheel (rota is Latin for wheel).
INTRODUCTION
First isolated in 1973 from children with
diarrhea
EM identification from duodenal biopsies
Human and animal strains are anti-genetically
distinct, and animal strains rarely cause
infection in humans.
INTRODUCTION CONT’
60-80nm in size
Non-enveloped virus Double capsid virus EM appearance of a wheel with
radiating spokes Icosahedral symmetry double stranded (ds) RNA in 11
segments
CLASSIFICATION
Groups, subgroups,
serotypes based on viral capsid proteins :
7 Groups (A through G)
Group A is the most common and has 2
subgroups
10 human serotypes based on G protein (VP 7)
Classification of rotaviruses is grouped into
serogroups and then serotypes , 7 antigenetically
different
sero-groups – A-G
Group A rotaviruses • Cause most human disease – Further subdivided into subgroups • Principal etiologic agent of severe gastroenteritis in infants and young children • Responsible for 1 billion cases of severe diarrhea • Major cause of mortality among the young
GROUP A ROTAVIRUSES Cause most human disease Further subdivided into subgroups • Principal etiologic agent of severe
gastroenteritis in infants and young children
• Responsible for 1 billion cases of severe diarrhea
Major cause of mortality among the young
OTHER ROTAVIRUSES • Group B – Adult diarrhea
• Group C – Primarily veterinary pathogens
• Groups D, E, F, G – Only known to infect animals
EPIDEMIOLOGY - WORLDWIDE
Millions are affected
600,000-850,000 deaths/year
A major cause of diarrhea-associated
hospitalizations
Seroprevalence studies show that
antibody is present in most by age 3.
ROTAVIRUS-WORLDWIDE DISTRIBUTION
Estimated Global Distribution of The 800,000 Annual Deaths
Caused By Rotavirus Diarrhea
. prevalent
area
EPIDEMIOLOGY : U.S
No. of children under 5y. affected ~ 2.7
million
Physician visits per year ~ 500,000
Hospitalizations per year ~ 50,000
Deaths per year ~ 20 - 40
% cases w/ dehydration ~ 1-2.5%
EPIDEMIOLOGY
Age- 4months - 2 years
Protection of younger infants through
transplacental antibody transfer
Asymptomatic infections are common,
especially in adults
Nosocomial infections
Outbreaks
EPIDEMIOLOGY
Seasonality
Winter months (Nov. through May in US)
Gradual spread W to E
Year-round in the tropics
Incubation period - thought to be <4 days
EPIDEMIOLOGYDIFFERENCES IN GROUPS
Group A infections are most common in human
Group B has been associated with outbreaks in adults in China
Group C is responsible for sporadic cases of diarrhea in infants around the world
PATHOGENESIS
Targeted host cells- mature enterocytes
lining the tips of intestinal villi
Intermediate/infective sub-viral particle
(ISVP) produced through proteolysis
enter host cell by endocytosis
ROTAVIRUS- EM STRUCTURE
ROTAVIRUS- 3D STRUCTURE
VIRAL STRUCTURAL PROTEINS (VP)
Outer structural proteins - VP7 and VP4
VP7VP7=glycoprotein
VP4VP4=protease-cleaved, P protein, viral
hemagglutinin, and forms spikes from the
surface
Inner core structural proteins VP 2, 3, 6
VP6 is an important antigenic determinant
VP4 determines how virulent the virus is
and it determines the P-type of the virus.
Genome is composed of 11 segments of double-
stranded RNA coding for six structural and five
nonstructural
proteins
Seven serological groups have been identified (A-G), three of which (groups A, B, and C) infect humans .
NONSTRUCTURAL VIRAL PROTEINS
NSP1, the product of gene 5, is a nonstructural RNA-binding protein.
NSP2 is an RNA-binding protein that accumulates in cytoplasmic inclusions (viroplasms) and is required for genome replication.
NSP3 is bound to viral mRNAs in infected cells and it is responsible for the shutdown of cellular protein synthesis.
NON STRUCTURE PROTEINS NSP4 is a viral enterotoxin to induce
diarrhoea and was the first viral enterotoxin discovered.
NSP5 is encoded by genome segment 11 of rotavirus A and in virus-infected cells NSP5 accumulates in the viroplasm.
NSP6 is a nucleic acid binding protein, and is encoded by gene 11 from an out of phase open reading frame.
ROTAVIRUS STRUCTURE
Gene coding assignment
ROTAVIRUS - PROPERTIES
Virus is stable in the environment
Relatively resistant to hand washing agents
Susceptible to disinfection with 95% ethanol,
‘Lysol’, formalin
REPLICATION There are two possible ways of entry in
the cell: Direct penetration of the virion across the
plasma membrane Endocytosis
EARLY EVENTS
Early transcription, translation, and assembly of double-layered particles.
Some of the (+) RNA that is synthesized functions as mRNA . NSP2 and NSP5 play roles in the assembly of viroplasms, where cores are assembled from VP1, VP2 and VP3.
Some of the (+) RNA functions as templates for synthesis of (−) RNA.
VP6 is added to the core to form a progeny double-layered particle.
LATE EVENTS
Late transcription, translation and virion assembly.
NSP4 is synthesized in the endoplasmic reticulum,where it binds VP4 and a double-layered particle .
This complex buds into the endoplasmic reticulum, where the final stages of assembly occur.
VP7, also synthesized in the endoplasmic reticulum, is added to form the outer
layer of the capsid and the VP4 spikes are added. Virions are released from the cell either by lysis or by
exocytosis
CLINICAL FEATURES
Incubation period - thought to be <4 days
Fever- can be high grade (>102F in 30%)
Vomiting, nausea precede diarrhea Diarrhea
- usually watery (no blood or leukocytes)
- lasts 3-9 days
- longer in malnourished and immune deficient indiv.
- NEC and hemorrhagic GE seen in neonates
HISTOPATHOLOGY
Mature enterocytes lining the tips of intestinal villi
are affected
Villous atrophy and blunting
Death of the mature enterocytes
HISTOPATHOLOGY
MECHANISM OF DIARRHEA Watery diarrhea due to net secretion of
intestinal fluid
Activation of the enteric nervous system -possible role of enterotoxin
CLINICAL FEATURES (CONTD.)(CONTD.)
Dehydration is the main contributor to mortality.
Secondary malabsorption of lactose and fat, and chronic diarrhea are possible
CONT’• Recovery is usually complete.
• However, severe diarrhea without fluid and electrolyte
replacement may result in dehydration and death .
Immunological Aspects
• Immunoglobulin (Ig A) , in the lumen of the gut immunity
to infection .• Actively or passively acquired antibodies (including antibodies
in
colostrum and mothers milk) lessen the severity of disease
but does not consistently prevent reinfection .• Absence of antibody small amounts of virus infection
and diarrhea .
DIAGNOSIS
Antigen detection in stool by ELISA, Latex
Agglutination (for Group A rotavirus)
EM- non-Group A viruses also
Culture- Group A rotaviruses can be
cultured in monkey kidney cells
Serology for epidemiologic studies
TRANSMISSION Mainly person to person via fecal-oral route
Fomites
Food and water-borne spread is possible
Spread via respiratory route is speculated
TREATMENT AND PREVENTION
Treatment Supportive - oral, IV rehydration
PreventionHand washing and disinfection of surfaces
ROTAVIRUS VACCINE• Rotarix which is the latest(licensed in 2008) RotaTeq(Rhesus rotavirus tetravalent vaccine) licensed
in 2006
– Serotypes 1, 2, 3, 4 for VP7
– Reassortant strains
– Protective against 80% of the cases of severe diarrhea, 100% of the dehydration cases
Rotashield
• Was recommended at 2, 4 and 6 months of age
• Risk of intussusception (a bowel blockage that is treated in a hospital and may require surgery) 1 in 12,274 infants
REFERENCES
Links: www.ncbi.nih.gov/pmc www.diarrhea.emedtv.com/rotavirus www.bvgh.org/biopharmaceutical www.pubmed.com www.cdc.comBook: Lange microbiology and Immunology review
(10th Edition)
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