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Lecture 3

Lecture 3 CSB351 Virology

2 Pages
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Department
Cell and Systems Biology
Course Code
CSB351Y1
Professor
Mounir Abou Haidar

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Virus is like a key fitting a lock (cell) --> virus is specific for target cells
{
Virus has its own glycoprotein attached to it
{
Only for enveloped virus: Envelope of virus: fuses with membrane of cell, virus gets in
{
+ RNA: RNA directly translatable by ribosome: ribo sees mRNA of the virus, binds to this, translates it--> converts into protein (AUG = start
protein, methionine)-->1st RNA translated: makes polymerase enzyme (which will go and copy out thousands of viral RNA)
¾
The large majority of DNA viruses: replicate in the nucleusof the cell (this is where DNA/chromosomes are, and where DNA-dependent
RNApolymerases are--> function is to synthesize mRNA)
¾
ALL DNA VIRUS (except for VACINEA?) replicate in the nucleus-->Go in there, use machinery of cell to make mRNA from DNA--> mRNA goes
into cytoplasm to be translated into viral protein
Most DNA viruses don't code for their own DNA-dependent RNA polymerase, because they know that the cell has them for its own
functions
¾
1 exception: Influenza virus -->go to nucleus for replication
Influenza virus wants to make machinery of the cell its slave! --> virus goes into nucleus, cuts off "cap" region of mRNA of the cell, put them
on their own mRNA --> steals their caps! (Other RNA viruses: polymerase synthesize their own caps)
Double-edged sword: cell's own mRNAs destroyed so cannot make its own protein, while lots of Influenza virus is being produced
Virus replicates once inside the cell--> replication depends on type of virus:
{
Recognition of target cell
1.
Attachment
2.
Penetration
3.
Uncoating
4.
Early mRNA& non-structural proteinsynthesis genes for enzymes and nucleic acid-binding proteins
|
Replication of genome: viral RNA/DNA
|
Late mRNAand structural proteinsynthesis (virus first needs to copy lots of RNA/DNA)
|
Posttranslational modification of protein (i.e. Glycoproteins--> have sugars added to them) -->Once you put sugar on a protein =
putting zip code on letter --> ships from Golgi out to the membrane of the cell
|
Viruses know how to use this for their own advantage
Macromolecular synthesis:
5.
Assembly: A few hours after infection: produce tons of nucleic acid--> packaged --> have virus assembly --> Lysis and release of virus from
cells
6.
Release of virus from cell: some bud (enveloped virus)/some lyse: destroys the cells (i.e. Cholera --> watery diarrhoea)
7.
Replication
(2) Page 6 Consequences of virus replication
Disease
When virus multiplies, uses cell machinery to make lots of copies
{
Cell dies --> virus infects surrounding cells --> soon all cells die then individual dies
{
Immune system: counteracts this via cell-mediated immunity
{
Virus Transmission
Hepatitis A: oral-fecal, transmitted via blood -->someone w/ HeptA goes to washroom, doesn't wash hands, goes to touch something, you
touch it and get virus -->virus goes into liver, makes liver sick --> disease because liver doesn't function properly-->Diseases: machinery of
the cell of an organ malfunctions
¾
Oral-fecal route: previously discusses
1.
Aerosols: sneezing (inhalation), crowding (sneezing spreads virus: breathe in by other people --> this is how influenza spreads), the most efficient
way it can spread
2.
Direct contact:
3.
Human papilloma virus (HPV)-->Cervix cancer (men sleeps with woman who has it, gives it to someone else when he sleeps with next person)
Similar: warts--> if you shake someone's hand and they have it, you'll get it too
Sexual transmission:
4.
HIV-1 (causes AIDS), genital Herpes, Hept B, C--> needs vaginal fluid OR blood-to-blood contact (i.e. Blood transfusion, organ transplant) -->*Anal
sex
Through insect bites:
5.
Mostly mosquitoes, ticks, etc --> Yellow fever, Rift Valley Fever Virus (West Nile), many encephalitis viruses
Mosquitoes: sucks blood from somebody--? HIV doesn't transmit by mosquitoes; viruses by mosquitoes: virus clutches to insect guts, goes back
to salivary gland of the insect, so when it feeds on the next human, goes into blood that way
Some viruses even replicate in mosquitoes (i.e. West Nile): every time it feeds on human etc, transmits virus to them
Direct inoculation: through bites
6.
Rabies virus through dog/bat bites ("punch a hole" straight into your muscles-->3-4 weeks later, virus goes into brain, fever, gone)
Through injection with needles Hepatitis B virus
When bitten: put salt on wound but still need vaccine
Only vaccine that works on virus: because of bitten period --> depends on where you are bitten --> if takes 3-5 months, take vaccine, build
immune system
Bitten in the face: doesn't take very long, but vaccinestill good treatment (virus can't get into brain, otherwise = death)
Blood transfusion and blood product:
7.
Hepatits C, HIV-1
Placental transmission:
8.
Rubella virus --> mother has disease, can transmit to baby (mother doesn't get affected but baby can have severe physical and mental
deformations)
The younger the babies, the worse the outcome (kills lots of cells in the baby)--> immune system does not recognize "self" :
Immune system: as a baby--> no antibodies (thus don't see Rubella virus and so no antibody against it)
Lecture 3
September-22-09
11:33 PM
CSB351 Course Notes Page 1
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Description
Lecture3 September-22-09 11:33PM { Virusislikeakeyfittingalock(cell)-->virusisspecificfortargetcells { Virushasitsownglycoproteinattachedtoit { Onlyforenvelopedvirus:Envelopeofvirus:fuseswithmembraneofcell,virusgetsin { Virusreplicatesonceinsidethecell-->replicationdependsontypeof virus: +RNA:RNAdirectlytranslatablebyribosome:riboseesmRNAofthevirus,bindstothis,translatesit-->convertsintoprotein(AUG=start protein,methionine)-->1stRNAtranslated:makespolymeraseenzyme(whichwillgoandcopyoutthousandsofviralRNA) ThelargemajorityofDNAviruses:replicateinthenucleusofthecell(thisiswhereDNAchromosomesare,andwhereDNA-dependent RNApolymerasesare-->functionistosynthesizemRNA) ALLDNAVIRUS (exceptforVACINEA?)replicateinthenucleus-->Gointhere,usemachineryofcelltomakemRNAfromDNA-->mRNAgoes intocytoplasmtobetranslatedintoviralprotein MostDNAvirusesdontcodefortheirownDNA-dependentRNApolymerase,becausetheyknowthatthecellhasthemforitsown functions ALLRNAviruses:dont go intonucleus 1exception:Influenzavirus-->gotonucleusforreplication Influenzaviruswantstomakemachineryofthecellitsslave!-->virusgoesintonucleus,cutsoffcapregionofmRNAofthecell,putthem ontheirownmRNA-->stealstheircaps!(OtherRNAviruses:polymerasesynthesizetheirowncaps) Double-edgedsword:cellsownmRNAsdestroyedsocannotmakeitsownprotein,whilelotsofInfluenzavirusisbeingproduced Replication 1. Recognitionoftargetcell 2. Attachment 3. Penetration 4. Uncoating 5. Macromolecularsynthesis: EarlymRNA& non-structuralproteinsynthesisgenesforenzymesandnucleicacid-bindingproteins Replicationofgenome:viralRNADNA LatemRNAand structural proteinsynthesis(virusfirstneedstocopylotsofRNADNA) Posttranslationalmodificationofprotein(i.e.Glycoproteins-->havesugarsaddedtothem)-->Onceyouputsugarona protein= puttingzipcodeonletter-->shipsfromGolgioutto themembraneofthecell Virusesknowhowtousethisfortheirownadvantage 6. Assembly:Afewhoursafterinfection:producetonsofnucleicacid-->packaged-->havevirusassembly-->Lysisandreleaseofvirusfrom cells 7. Releaseofvirusfromcell:somebud(envelopedvirus)somelyse: destroysthecells(i.e.Cholera-->waterydiarrhoea) (2)Page 6 Consequences of virus replication Disease { Whenvirusmultiplies,usescellma
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