family caliciviridae: noroviruses
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FAMILY CALICIVIRIDAE:FAMILY CALICIVIRIDAE:NorovirusesNoroviruses
To Be Discussed:To Be Discussed:
Taxonomy, structure and genomeTaxonomy, structure and genome
Disease manifestations and clinical symptomsDisease manifestations and clinical symptoms
DiagnosisDiagnosis
TransmissionTransmission
Epidemiology and incidence Epidemiology and incidence
Environmental resistanceEnvironmental resistance
Prevention and ControlPrevention and Control
Noroviruses TaxonomyNoroviruses Taxonomy
Previously- Family CaliciviridaePreviously- Family Caliciviridae
Genus:Genus: 1. Norwalk-Like Viruses (NLVs)1. Norwalk-Like Viruses (NLVs)
2. Sapporo-Like Viruses (SLVs)2. Sapporo-Like Viruses (SLVs)
Recently- Genus NorovirusesRecently- Genus Noroviruses
(formerly Norwalk-Like Viruses)(formerly Norwalk-Like Viruses)
The Norovirus GenusThe Norovirus Genus
Norwalk VirusNorwalk Virus
Desert Storm VirusDesert Storm Virus
Southampton VirusSouthampton Virus
Snow Mountain AgentSnow Mountain Agent
Hawaii VirusHawaii Virus
Toronto VirusToronto Virus
Bristol VirusBristol Virus
Jena VirusJena Virus
Viral MorphologyViral Morphology
Non-enveloped, icosahedralNon-enveloped, icosahedral
27-40 nm27-40 nm
Single structural capsid protein, 60kDSingle structural capsid protein, 60kD
- 180 molecules, folds into 90 - 180 molecules, folds into 90 dimers dimers
Distinguishing characteristic:Distinguishing characteristic:
32-cupped shaped depressions on the 32-cupped shaped depressions on the axes of the icosahedronaxes of the icosahedron
Norovirus Structure by EM
www.pubmed.gov PMID: 13679618
GenomeGenome(+) ss RNA, 7900 nt in length(+) ss RNA, 7900 nt in length
3 Open Reading Frames:3 Open Reading Frames:
ORF1= non-structural proteins- RdRp ORF1= non-structural proteins- RdRp + helicase + helicase
ORF2= structural capsid proteinORF2= structural capsid protein
ORF3= small protein, function unknownORF3= small protein, function unknown
5’ 3’
ORF1 ORF2 ORF3
RdRp hel cap ?
GenomeGenome
www.pubmed.gov; PMID: 13679618
www.allthevirologyonthewww.com
RdRp StructureRdRp Structure
Crystal structure from www.pubmed.gov PMID: 12706072
Replication StrategyReplication StrategyReplication suggested- Typical of positive-sense ss RNA viruses, unconfirmedReplication suggested- Typical of positive-sense ss RNA viruses, unconfirmed
Wagner et al. Basic Virology. www.netlibrary.com
Replication of the GenomeReplication of the Genome
Wagner et al. Basic Virology. www.netlibrary.com
Disease ManifestationsDisease Manifestations
Infects small intestines and causes Infects small intestines and causes gastroenteritisgastroenteritis
Expansion of the villi at proximal small Expansion of the villi at proximal small intestine and shortening of the microvilli intestine and shortening of the microvilli
-epithelial cells remain intact-epithelial cells remain intact
Incubation period: 24-48 hoursIncubation period: 24-48 hours
Mistakenly termed- “stomach flu”Mistakenly termed- “stomach flu”
Path of InfectionPath of Infection
Wagner et al. Basic Virology. www.netlibrary.com
Clinical SymptomologyClinical SymptomologyNon-bloody diarrheaNon-bloody diarrhea NauseaNausea
VomitingVomiting Abdominal crampsAbdominal cramps
MalaiseMalaise MyalgiasMyalgias
HeadacheHeadache Low-grade feverLow-grade fever
Symptoms last 12-60 hours.Symptoms last 12-60 hours.
Children tend to suffer from vomiting, while Children tend to suffer from vomiting, while adults tend to suffer from diarrhea.adults tend to suffer from diarrhea.
TransmissionTransmissionFecal-Oral Fecal-Oral Typically in contaminated drinking waterTypically in contaminated drinking waterMany sources found : Many sources found :
poorly maintained municipal poorly maintained municipal suppliessupplies
wellswellsrecreational lakesrecreational lakesswimming poolsswimming poolscruise ship watercruise ship waterfood handled by infected person or food handled by infected person or washed with contaminated waterwashed with contaminated water
Prevalence of Sources of TransmissionPrevalence of Sources of Transmission
Epidemiology and IncidenceEpidemiology and Incidence
Found Worldwide.Found Worldwide.
Burden: - ca. 267,000,000 annual casesBurden: - ca. 267,000,000 annual cases
- 612,000 hospitalizations- 612,000 hospitalizations
- 3,000 deaths- 3,000 deaths
Highly contagious: fewer than 100 virus Highly contagious: fewer than 100 virus particles can cause infectionparticles can cause infection
2002- Cruise ship bound for Alaska-2002- Cruise ship bound for Alaska-
13% of 1266 on board were 13% of 1266 on board were affected; contaminated drinking affected; contaminated drinking waterwater
EpidemiologyEpidemiology
Frankenhauser et al. www.cdc.gov
Prevention and ControlPrevention and Control
Highly Stable in environment-Highly Stable in environment-
resistant to: resistant to:
freezingfreezing
heating to 60heating to 60ºCºC
disinfection w/ chlorinedisinfection w/ chlorine
acidic conditionsacidic conditions
vinegarvinegar
alcoholalcohol
high sugar high sugar concentrationconcentration
Prevention and ControlPrevention and ControlInfection produces IgG, IgA and IgM, but Infection produces IgG, IgA and IgM, but antibodies are not protective.antibodies are not protective.No lasting immunity or protection from No lasting immunity or protection from reinfection. Transient immunity- lasting 3-4 reinfection. Transient immunity- lasting 3-4 months.months.Vaccine not likely.Vaccine not likely.No current antiviral drugs, however complete No current antiviral drugs, however complete recovery is most common.recovery is most common.Prevent by hand-washing, good hygiene, proper Prevent by hand-washing, good hygiene, proper water management, preparation of food.water management, preparation of food.
Things to Remember for ExamThings to Remember for Exam
Defining structural characteristic(s).Defining structural characteristic(s).
Nucleic acid/ genome type.Nucleic acid/ genome type.
How many open reading frames and what How many open reading frames and what each one contains (general).each one contains (general).
Cell tropism and effects; hint- Does Cell tropism and effects; hint- Does Norwalk virus kill intestinal epithelial cells?Norwalk virus kill intestinal epithelial cells?
Infectious dose; environmental stabilityInfectious dose; environmental stability
Lasting immunity?; protective antibodies Lasting immunity?; protective antibodies produced?produced?
ReferencesReferences
Centers for Disease Control and Prevention. “Norwalk-Like Viruses:” Centers for Disease Control and Prevention. “Norwalk-Like Viruses:” Public health consequences and outbreak management. MMWR Public health consequences and outbreak management. MMWR 2001; 50 (No. RR-9): [inclusive page numbers]. www.cdc.gov 2001; 50 (No. RR-9): [inclusive page numbers]. www.cdc.gov
- MMWR, 2003, Outbreaks on Cruise ships.- MMWR, 2003, Outbreaks on Cruise ships.
www.pubmed.gov suggested articles, PMID: 13679618; 14499247; www.pubmed.gov suggested articles, PMID: 13679618; 14499247; 14557646; 14715308; 12791850; 1270607214557646; 14715308; 12791850; 12706072
Wagner, E.K.; Martinez, H. Wagner, E.K.; Martinez, H. Basic VirologyBasic Virology. Malden, MA. Blackwell . Malden, MA. Blackwell Science, 1999. www.netlibrary.com Science, 1999. www.netlibrary.com
Dorlands Online Medical Dictionary. www.dorlands.com Dorlands Online Medical Dictionary. www.dorlands.com
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