MIMM 465 Lecture Notes - Lecture 6: Entamoeba, Syncytium, Common Cold

60 views10 pages
Published on 16 Apr 2013
School
McGill University
Department
Microbiology and Immun (Sci)
Course
MIMM 465
Lecture 6
<Viral diarrhea Dr. Liang>
Contents
- Gastroenteritis
Viral gastroenteritis (4 viruses causes gastroenteritis
- Rotavirus major cause of viral diarrhea in young children (also high mortality)
- Norovirus major cause of viral diarrhea in ALL ages
Gastroenteritis: an acute infectious syndrome of the stomach lining and the intestine
- Syndromes: diarrhea, vomiting, abdominal pain, nausea, fever and chills
- Causes can be infection by:
Viruses rotavirus, adenovirus, calicivirus, astrovirus
Bacteria E. coli, salmonella, shigella and cholera
Parasites Giardia lamblia, Entamoeba histolytica and Cryptosporidium
- Gastroenteritis is triggered EITHER by
1. Toxins that are secreted by microbes and lead to excessive loss of water and electrolytes OR
2. By direct invasion of the wall of the gut by microbes, followed by inflammation
- Inflammation gives the symptoms of diarrhea
- Transmission: highly contagious, oral-fecal route
Impacts:
- >2 million deaths annually, second only to pneumonia for children under 5 yrs of age
- 1 in 200 children who contract diarrhea die from it = high mortality in children
- 4,500 children die of diarrhea every day in low-income countries
Mortality caused by acute diarrheal disease
- Pie chart from WHO
- Rotavirus (860,000) > Typhoid (600,000) > Shigella (600,000) > ETEC (380,000) > Cholera (120,000)
Except for rotavirus, rest are bacteria
- Total deaths: 2.5 million (mostly in young children)
Treatment:
- Mostly resolve w/o specific treatment
- Reduce symptoms and prevent dehydration
- Tips for treatment
Allow gastrointestinal tract to settle by not eating for a few hours.
Sip small amounts of clear liquids or suck on ice chips if vomiting is still a problem.
Give infants and children oral rehydration solutions to replace fluids and lost electrolytes.
Gradually reintroduce food, starting with bland, easy-to-digest food, like toast, broth, apples, bananas, and rice.
Avoid dairy products, caffeine, and alcohol until recovery is complete.
Get plenty of rest.
Prevention: washing hands!!!
- Wet hands soap (20seconds) scrub backs of hands, writs, b/w fingers and under fingernails rinse towel
dry turn off taps with towel
Acute gastroenteritis viruses:
- Rotavirus: leading cause among children 3-15 months old, also infect adults
- Adenovirus: mainly infect children under 2 yrs of age, one of the 49 types of adenovirus affects gastrointestinal tract
- Caliciviruses: infect people of all ages, the most common cause, and Norovirus infection leads to epidemic
The most common cause of viral diarrhea
- Astrovirus: primarily infects infants, young children and elderly
In people with weak immune system
Unlock document

This preview shows pages 1-3 of the document.
Unlock all 10 pages and 3 million more documents.

Already have an account? Log in
Rotavirus (morphology of ‘wheel’)
- Belongs to Reoviridae
There are quite a few number of other family under Reoviridae
- Infect gastrointestinal and respiratory tracts (ALL the tract we have to digest the food and breathe)
- Non-enveloped particles
- Icosahedral capsid (T = 13) with an outer and inner protein shell
- 11 segments dsRNA genome
ALL Reoviridae have dsRNA genome
- Species A to G (7 species), rotavirus A causes >90% of the infections
- Transmission: fecal-oral route
- Tissue tropism: small intestinal enterocytes
- Mainly infect infants and young children.
>500,000 children under 5 yrs of age die of rotavirus infection in low income countries, per year
- Prevention and treatment: vaccines and oral rehydration (no special treatment)
Rotavirus vaccines
- The first rotavirus vaccine Rotashield was licensed in 1998, was unfortunately withdrawn from market due to the
increased risk for intussusception (1 in 12,000 vaccinated infants) = sharp pain in the intestine
- In 2006, two new vaccines against rotavirus A were tested to be safe and effective.
These are rotarix by GlaxoSmithKline and RotaTeq by Merck.
In 2009, WHO recommended inclusion of these two rotavirus vaccines in national immunization program.
11 RNA segments of rotavirus
- Each segment encode one viral
protein except for segment 9 and 11
- Alternative initiation of translation
in segments 9 and 11 = translate two
different proteins
- VP: structural protein
- NS: non-structural protein (not
involved in virus particle assembly)
Proteins and basic functions
- NSP4, translated from segment 10
It is an enterotoxin, that cause diarrhea
symptom
If you can neutralize this toxin, you can
relieve such symptom
Structure of rotavirus particles
- Two shells inner and outer shells
- Outer layer VP4 and VP7
- Middle layer of the outer shell VP6
- Inner layer VP2
- VP1 and VP3 form a channel
Unlock document

This preview shows pages 1-3 of the document.
Unlock all 10 pages and 3 million more documents.

Already have an account? Log in
VP1 and VP3 are responsible for transcribing viral RNA and add 5’ cap to the RNA RNA could leave into
the cytosol to make viral protein and viral genome
- dsRNA NEVER leave the core
Rotavirus life cycle
- Many details are quite unknown
- Viral particle has 3 layers Outer, middle
and inner layer with spikes on the surface
- Following the entry, transcription (+)
strand RNA occurs these can be used to
make viral proteins viral proteins can be
assembled to form the core structure
- RNA’ll be converted into dsRNA inside
the core
- The particle will mature virion
assembly at ER membrane leave the cell
Entry:
- VP4 and VP7 = spike
- VP4 is cleaved into VP8* (aa 1-247) and VP5* (aa 248-776)
VP8 and VP5 ARE NOT directly made from viral RNA
VP8: binds to sialic acid
VP5: binds to integrins
There are two receptors, sialic acid and integrin that are needed for the rotavirus to enter the cell
- Entry leads to the loss of outer layer, release of DLPs (double layered particles) into the cytoplasm;
This uncoating process can be recapitulated by treating virus particles with calcium chelators, such as EDTA
- Can destabilize the outer layer
RNA transcription (I)
- VP6 form the intermediate layer to coordinate the outer layer (VP7) and the inner layer (VP2);
- 260 trimers of VP6 form a T=13 icosahedral capsid with 132 aqueous channels spanning the VP7 and VP6 layers
This channel is used so the viral RNA could leave to the host cytoplasm
- DLPs are transcriptionally competent
- RNA transcripts exit from the channels
RNA transcription (II)
- The inner core contains VP1, VP2 and VP3
- 60 dimers of VP2 form the shell structure with 12
five-fold axis, is the only viral protein with self-
assembly property
- VP1 is the RdRP, VP3 is guanylyl and methyl
transferase
VP3 responsible for adding 5’ cap to the
mRNA
RNA transcription (III)
- Packing of viral RNA segments w/in the VP2
capsid
RNA transcription (IV)
- Structure of VP1 (RdRP) DIAGRAM ON RIGHT
It has four channels
dsRNA’s 5’ cap is anchored on the surface
of the polymerase dsRNA separates into
two single strands (-) strand will go into
one channel and (+) strand to another
channel
(-) strand is used to make more (+) strand RNAs
Unlock document

This preview shows pages 1-3 of the document.
Unlock all 10 pages and 3 million more documents.

Already have an account? Log in

Document Summary

Rotavirus major cause of viral diarrhea in young children (also high mortality) Norovirus major cause of viral diarrhea in all ages. Gastroenteritis: an acute infectious syndrome of the stomach lining and the intestine. Syndromes: diarrhea, vomiting, abdominal pain, nausea, fever and chills. Bacteria e. coli, salmonella, shigella and cholera. Parasites giardia lamblia, entamoeba histolytica and cryptosporidium. Gastroenteritis is triggered either by: toxins that are secreted by microbes and lead to excessive loss of water and electrolytes or, by direct invasion of the wall of the gut by microbes, followed by inflammation. >2 million deaths annually, second only to pneumonia for children under 5 yrs of age. 1 in 200 children who contract diarrhea die from it = high mortality in children. 4,500 children die of diarrhea every day in low-income countries. Rotavirus (860,000) > typhoid (600,000) > shigella (600,000) > etec (380,000) > cholera (120,000) Total deaths: 2. 5 million (mostly in young children)

Get OneClass Grade+

Unlimited access to all notes and study guides.

YearlyMost Popular
75% OFF
$9.98/m
Monthly
$39.98/m
Single doc
$39.98

or

You will be charged $119.76 upfront and auto renewed at the end of each cycle. You may cancel anytime under Payment Settings. For more information, see our Terms and Privacy.
Payments are encrypted using 256-bit SSL. Powered by Stripe.