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71 Cards in this Set
- Front
- Back
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What is gastroenteritis?
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An acute infectious syndrom of the stomach lining and the intestine
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What are the syndromes that are caused by gastroenteritis?
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Diarrhea
Vomiting Abdominal pain Nausea Fever Chills |
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What can cause these infections?
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Viruses: rotavirus, adenovirus, calcivirus, astrovirus
Bacteria Parasites |
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What triggers gastroenteritis?
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1- The toxins that are secreted by microorganisms and lead to excessibe loss of water and electrolytes
2- Direct invasion of the wall of the gut followed by inflammation |
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How is this transmitted?
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Highly contagious
Oral-fecal route |
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What's the impact of gastroenteritis?
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>2 million deaths annually (only 2nd to pneumonia for kids under 5)
1 in 200 children who contract diarrhea and die from it 4500 children die of diarrhea everyday |
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What are the main agents responsible for acute diarrheal disease?
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Rotavirus > Shigella = typhoid > ETEC > Cholera
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What is the treatment for viral diarrhea?
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Most resolve without specific treatment
Reduce symptoms and prevent dehydration |
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What are some tips to help with diarrhea?
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Allow GIT to settle a bit
Drink clear liquids Give children/infants oral rehydration solutions to replace fluids and lost electrolytes Gradually reintroduce food Avoid dairy products, caffeine and alcohol Rest |
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What is the best prevention?
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Hand washing
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What are the 4 acute gastroenteritis viruses?
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Rotavirus
Adenovirus Calicivirus Astrovirus |
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Who does Rotavirus infect?
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Leading cause among children 3-15 months old
Also infects adults |
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Who does Adenovirus infect?
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Mainly infect children under 2
One of 49 types of adenovirus affeccts GIT |
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Who do Calciviruses infect?
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Infect ppl of all ages, the most common cause of viral diarrhea
Norovirus infection leads to epidemic |
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Who does the astrovirus infect?
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Primarily infants, young children and the elderly
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Describe the rotavirus
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11 segments
dsRNA genome Non-enveloped particles Icosahedral capsid T=13 Outer an inner ptn shell (2 shells) |
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How many species does Rotavirus have?
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7 species (A-G)
>90% of the infections |
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How is the rotavirus transmitted?
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Fecal-oral
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What is the tissue tropism of rotavirus?
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Small intestinal enterocytes
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Who does Rotavirus mainly infect?
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Infants and young children
>500,000 children under 5 are currently infected |
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How can Rotavirus be prevented/treated?
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Vaccines
Oral rehydration |
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What does the rotavirus look like?
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A wheel
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What does the rotavirus viral ptn NSP4 do?
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Acts as enterotoxin that cause loss of H2O and electrolytes
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What happens when Rotavirus infects?
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Virus destroys cells and get inflammation
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Why was the 1st rotavirus vaccine withdrawn from the market?
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Caused increased risk of intussusception
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What are the current vaccines for rotavirus?
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Rotarix
RotaTeq |
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How many RNA segments does the rotavirus have?
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11
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How many ptns does each RNA segment encode?
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Each encodes 1 ptn
Except segments 9 and 11 which can make 2 ptns each ->Depends on alternative initiation |
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Describe the structure of rotavirus particle
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Outer layer: VP4 and 7
Middle layer: VP6 Inner layer: VP2 |
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Describe the outer layer
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Made of VP4 and 7
VP4 turned outwards, rec'z and binds viral receptors on ell surface and mediates entry |
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Describe the middle layer
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VP4
Arrayed as a hexamer |
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What is under the inner layer (VP2)?
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VP1/3
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What is VP1?
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RdRPol
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What is VP3?
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Adds cap to viral mRNA
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What happens when viral mRNA is made?
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Goes from under the inner core (under VP1/3|) and goes through the tunnel made by VP2/6
dsRNA to replicate/synthesixe Genome never leave the core because dsRNA will be rec'z by IR and killed |
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Describe Rotavirus entry
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VP4 is cleaved into VP8 (aa 1-247) and VP5 (aa 248-776)
VP8 interacts with sialic acid VP5 interacts with integrins Entry leads to the loss of outer layer Release of DLPs omtp tje cytoplasm Uncoated process can be recapitulated by treating virus particles with Ca chelators like EDTA |
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What is the receptor for VP8?
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Sialic acid
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What is the receptor for VP5?
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Integrins
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Describe RNA transcription of rotavirus
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VP6 makes the intermediate layer to coordinate the outer layer (VP7) with the inner layer (VP2)
260 trimers of VP6 for T=13 icosahedral capsid, with 132 aqueous channels, spanning the VP7/6 layers DLPs are transcriptionally competent RNA transcripts exit from the channels Inner core contains VP1/2/3 60 dimers of VP2 form the shell structure with 12 five-fold axis, us tge ibly viral ptn with self-assembly property VP1 is a RdRPol, VP3 is a guanylyl and methyl transferase Packaging of viral RNA segments within the VP2 capsid |
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Is the capsid tightly packed?
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Yes
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Describe VP1
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Has a RH configuration
Has long NTD and CTD |
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Describe the structure of VP1
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4 channels
2: one are for entry sites for RNA template, one for NTPs 2: Exit for templates (-) RNA/dsRNA or Exit for (+) RNA/mRNA |
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Describe the Norovirus
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Most common cayse of viral gastroenteritis
Accounts for 90% of non-bacterial outbreaks of gastroenteritis |
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What are the 4 species of calciviridae?
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Norovirus
Sapovirus Vesivirus Lagovirus |
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Describe the calciviridae
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Non-enveloped
Icosahedral virus 38 nm diameter (very small) +ssRNA |
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Why is it hard to make antivirals/vaccines against this virus?
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Lack of reliable cell culture system and small animal models
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What is the natural host of norovirus?
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Humans only
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How many gps is the norovirus divided into?
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5 genogps (GI-GV)
->Share 51-56% genomic nucleotide similarity Each genogp is divided into dif genotypes, share 69-97% genomic nucleotide similarity |
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How many genotypes does G1 have?
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8
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How many genotypes does GII have?
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17
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Which genotype accounts for most norovirus outbreaks?
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GII.4 account for 70-80% of the outbreaks
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What is the prototypical norovirus?
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Norwalk virus (GI.1-NV)
->1sr isolated viral agent causing diarrhea |
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Describe the outbreaks of noroviruses in the US
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Used to be caused by any GII except GII.4
Is now caused by GII.4 |
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What are some feature of norovirus infection?
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Highly contagious
Viral shedding precedes the onset of illness and continue shedding long after the illness Can withstand a wide range of Temp Great diversity of the virus, lack of cross-protection and long term immunity Easily undergoes mutation |
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What does norovirus infection cause?
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Sudden onset of vomiting and diarrhea
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How many ORFs does norovirus have?
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3
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What do these ORFs encode?
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ORF 1: Carries enz virus needs to replicate
ORF 2 & 3: Has VP 1& 2, building VP |
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Does norovirus have an env?
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No
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What can VP1 and 2 do?
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Without anything else, VP1&2 can make VLPs
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What are the 3 domains of VP1?
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P1
P2 S -->P1/2 induce folding |
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What is the P2 site?
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Site where cellular receptor binds
Highly diverse |
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What do people who are naturally resistant to norovirus infection have?
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Have polymorphism of histo-bld gp Ag (HBGAs)
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What are the HBGAs for?
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Receptors of norovirus
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What % of Europeans who are nonsecretors are resistant to infection with Norwalk virus?
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20%
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What do nonsecretors have that are missing?
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Don't have a fctnal fucosyltransferase 2 gene
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What do naturally resistant ppl have?
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No H Ag for NV binding
No viral shedding No serum or Ab response |
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What happens to the susceptible population (80% of the pop'l)?
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45% are infected:
-Viral shedding -50% are symptomatic -Late (>day5) serum IgG response -Late mucosal NV IgA specific response Protected 35%: -No viral shedding -No symptomatic disease -No serum IgG response -Early (<day5) IgA mucosal response |
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What family do HBGAs belong to?
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Family of complex glycans that are expressed on the surface of RBCs, gut and respiratory epithelial and biological secretions in humans
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What are the 3 major HBGAs?
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ABO
Lewis family Secretor family ->All involved in binding norovirus |
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What decides where HBGAs will bind the virus?
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P2 on VP1
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Is binding of HBGAs the same for GI and GII?
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No, very different
-->Only see consensus within the GI genotypes -->In GII, aa have been changed, bind another type of HBGAs -->Complicated to eradicate norovirus |
