TRNG H KHOA HC KHOA KHOA HC S SNG

GIO N VI SINH VT
GV: Trnh Ngc Hong

Thi Nguyn - 2011

BI 7. VIRUS

MT S BNH DO VIRUS
CM AIDS U MA QUAI B

DI

SI

VIM NO NB

VIM GAN

BI LIT

VIM MNG NO

Ni dung
1 Lc s nghin cu virus Hnh thi, cu trc ca virus

2 3 4

Cc phng thc sinh sn virus Cc nhm virus chnh

I. LC S NGHIN CU VIRUS
1882
L. Pasteur Ch c vacine phng di t no ch

1892

Ivanowsky

1915

W. Twort Pht hin ra virus vi khun: phage

1918

I. LC S
1934-38
Pht hin ra virus vim no Nht bn

1935

Stanley

1954

Tm ra virus cm H2N2

1958

I. LC S
1976
Virus Ebola c m t ln u

1983

2003

Bng pht dch Sar: vim ng h hp cp

2004

NH NGHA
Virus l mt sinh vt phi t bo, siu hin vi, ch cha 1 loi axit nucleic. Chng k{ sinh bt buc trong t bo sng, da vo s hip tr ca h thng trao i cht ca vt ch m sao chp axit nucleic, tng hp cc thnh phn nh protein sau tin hnh lp ni sinh sn; trong iu kin ngoi c th chng c th tn ti lu di trng thi i phn t ha hc khng sng v c trng thi truyn nhim GS. Chu c Khnh H Phc n, Trung Quc

C IM
- Cha c cu to t bo
- Vt cht di truyn l DNA/ RNA - Kch thc cc kz nh b - lt qua mng lc vi khun (ch quan st c di KHV in t ) - Virus bt buc phi sng k{ sinh trong t bo sng, l yu t gy nhim bt buc trong t bo ch , (khng c c quan to nng lng (ATP), khng c tt c cc loi enzim t nhn ln duy tr chu kz sng)

II. HNH THI V CU TRC CA VIRUS

1. KCH THC
- Rt nh b, lt qua mng lc vi khun - Ch quan st c di KHV in t (c nm) + Virus u ma c kch thc ln nht (250nm ???) v virus nh nht l virus thuc h Picornaviridae, c kch thc khong 10-20nm. Loi virus Virus ARN Virus ADN Phage Kch thc trung bnh (nm) 20 - 300 18 - 300 10 - 150

1. KCH THC

2. HNH THI
- Virus hon chnh (virion) = (RNA/DNA) + v protein (capside) + Mt s loi virus c thm v ngoi - Hnh thi ca virus do v capside hoc v ngoi quyt nh

Cu

Que

Khi

c bit

2. HNH THI

i xng xon

Virus gy bnh cho thc vt nh (virus m thuc , khoai ty) Hnh que di

i xng 20 mt

Gn ging hnh cu Phn ln l virus ng vt.

i xng phc tp

Virus ca vi khun (phage) Kch thc 10 150 nm

Mt s dng hnh thi ca virus

3. CU TRC V CAPSID
- Capsid c cu to t cc n v hnh thi (VHT) gi l capsome - Capsid c kh nng chu nhit, pH v cc yu t ngoi

cnh nn nhm bo v li axit nucleic.

- Trn mt capsid cha cc gai glycoprotein hoc lipoprotein l cc th th c hiu gip cho virus bm vo cc th th c hiu trn b mt t bo vt ch. - Cu trc in hnh cu virus: i xng

3.1 Cu trc i xng xon

- S d virus c cu trc dng ny do cc capsome sp xp theo chiu xon ca axit nucleic. - Cu trc xon lm cho virut thng c dng hnh que hay hnh si. in hnh l cc virut m thuc l (TMV), di (rhabdo), quai b, si (paramyxo), cm (orthomyxo)

TMV (Tobaco mosaic virus) + TMV c dng hnh ng rng ng knh 15nm, di 300nm do c cu trc i xng xon tr. Trong 95% l Protein, 5% l ARN xon c.
+ Thnh ng bao gm 2600 VHT cu to t mt loi protein duy nht hnh chic giy, cha 158 axit amin, ghp i xng vi nhau thnh nhiu vng xon, gn thnh hnh ng di. Ton b ng c 162 vng xon.

TMV (Tobaco mosaic virus)

+ Axit nucleic ca TMV l mt si ARN 1 mch chim 5% trng lng ht, un theo chiu xon ca capsid, gn vo 2/3 chiu di bn trong ca capsid. + Trong 6000 nucleic trn phn t ARN ca TMV ch c 474 nucleic l m ho cho qu trnh to v capsit ca n.

TMV (Tobaco mosaic virus)

TMV.

Cu hi ?

Cu to phng to ca virus TMV lm bn lin tng ti hnh nh g ???

TMV chng ?

3.2 Cu trc i xng khi

- Nhiu loi virut nhn qua c dng hnh cu nh: Adeno, Polio, Picorna, Herpes nhng quan st di KHV in t cho thy v protein capsid ca chng c cu trc hnh khi a din, thng l cc hnh khi 20 mt u (Icosahedron).

- Cu trc Icosahedron l mt hnh khi a din 20 mt tam gic u: 5 mt nh, 5 mt y, 10 mt gia, cc tam gic u nhau v i xng, c th sp xp theo bt kz hng no. Icosahedron phc tp c v bc bao ngoi vi cc gai nh trn b mt.

Icosahedron

Adenovirus

3.3 Cu trc phc tp

- cc VR k sinh trn VK (phage), chng c hnh nng nc vi hai kiu i xng phc tp. Trong cc phage k sinh trn E.coli th phage T2 v T4 c nghin cu t m nht.

Hai kiu i xng ca phage T2 l g ?

Phage T2

- T2 hnh nng nc, u di 100nm, u bng ui, u hnh lc lng ng knh 65nm, bn trong l DNA 2 mch cun li thnh bi.
- ui c cu trc phc tp di 120nm, ng knh 25nm, bn trong l tr ui hnh ng ng knh 15nm, cng nh kim tim, dng ph v t bo ca VK ch. Bn ngoi tr ui l protein c cu trc i xng xon tr nh TMV, c kh nng co dn, c cu to t 24 vng xon bao quanh trc ui, mi vng xon cha 6 VHT cu to t 144 phn t protein cng 1loi.

4. V NGOI (ENVELOPE)
- Cu trc xon, khi, phc tp ca VR c th dng trn hoc c lp mng bao bc bn ngoi capsid - Bn cht ca v ngoi + lipoprotein v cc gai nh ca n xuyn ra t lp protein qua lp mng lipopotein + glicoprotein cha cc th th hoc enzim ca cc virus , va l khng nguyn, bo v li axit nucleic ca virus v gip chng bm vo mng t bo ch (thng gp VR V).

- V ngoi c ngun gc t mng sinh cht (HIV) hoc mng nhn (Herpes), hoc t Golgi (Pox virus) ca t bo ch c virus cun theo khi ny chi.

V NGOI

- Di tc dng ca mt s yu t nh dung mi ho tan lipit, enzim v ngoi b bin tnh v virus c th khng cn kh nng ly nhim.
- V ngoi c tc dng lm n nh cu trc ca ht virus.

5. CU TRC AXIT NUCLEIC

- Axit nucleic ca virus c th l si DNA/ RNA - Si n (ss) hoc kp (ds) - Mch thng hoc vng, cu trc lin tc hoc t thnh nhiu on ring r.

DNA strand
*) Chui n - ss DNA +) si thng ss DNA Vd: Parvoviridae

+) vng ss DNA
Vd: phage X 174, M13 ca E. coli

DNA strand
*) Chui kp - ds DNA +) si ds DNA Vd: Adenovirus, Herpes virus Pox virus - Thng c kch thc ln nht trong cc virus +) vng ds DNA Vd: phage ca E. coli, Papovaviridae

RNA strand
*) Chui n - ss RNA - Chim hu ht cc h virus chnh Vd: Picornaviridae, orthomyxoviridae, paramyxoviridae, rhabdoviridae, Retroviridae, TMV

*) Chui kp - ds RNA
Vd: Reoviridae

III. CC PHNG THC SINH SN CA VIRUS

III. CC PHNG THC SINH SN

Vt ch ca virus
- ng vt

- Thc vt
- Vi khun - Khc: nm, VNS *) Vi cc vt ch khc nhau, virus c phng thc sinh sn khc nhau

III. CC PHNG THC SINH SN

Virus ch c th nhn ln trong t bo cm th (t bo b virus xm nhp), nh hot ng ca t bo m virus thc hin s tng hp cc thnh phn to thnh cc ht virus mi.

Qu trnh nhn ln bt u t lc virus hp ph ln b mt ca t bo cho n lc virus trng thnh chui ra khi t bo.
Ton b qu trnh nhn ln ca virus chia ra lm 5 giai on

III. CC PHNG THC SINH SN

Sinh sn ca virus:

- Sao chp axit nucleic + tng hp protein Virion

5 giai on: 1. Hp ph 2. Xm nhp 3. Sao chp 4. Thnh thc 5. Phng thch

Phage cycle

Chu kz nhn ln ca virus vi khun

Giai on 1. Giai on hp ph ca virus ln b mt t bo

Cc ht virus quanh t bo lun trng thi chuyn ng, chng va chm ln b mt t bo, gip virus tm t bo cm th, trn b mt ca t bo cm th li c nhng th th (receptor) c hiu cho cc v tr cu trc c hiu trn b mt ht virus gn vo th th. Qu trnh hp ph ca virus vo t bo quyt nh bi mi tng tc gia th th ca virus vi th th ca t bo. S hp ph ny ch xy ra khi 2 th th ca virus v t bo hon ton khp nhau, nh kha vi cha kha. iu gii thch v sao mi loi virus ch c th hp ph v gy nhim cho mt loi t bo nht nh, v d virus thc vt khng bao gi gy nhim cho t bo ng vt c xng sng.

Giai on 2. Giai on xm nhp Virus xm nhp vo t bo theo 2 c ch: - Vi i a s virus: Cc t bo mc ra chn gi bao vy ly virus, ri khp li, a virus vo bn trong t bo theo kiu amp bt mi, ngi ta gi hin tng ny l m bo. Sau khi virus vo t bo, virus khng t lt v c m phi nh t bo tit ra enzym decapsidae ci b v capsit ca virus v axit nucleic ca virus c gii phng khi virus.

- i vi thc khun th. Vi phage T (ca vi khun E.coli) sau khi ui ca phage hp th ln b mt ca t bo, chng tit ra cht lyzozim lm tan mng t bo vi khun, sau di tc dng ca adenosine triphosphatase (ATP) ui phage co li v tr chc thng mng nguyn sinh cht ca t bo, axit nucleic c bm vo trong t bo theo tr ng, cn phn protein v bc th nm bn ngoi mng t bo v khng tham gia vo qu trnh ti to ht virus mi.

Giai on 3. Giai on tng hp cc thnh phn ca virus

Ngay sau khi virus xm nhp vo trong t bo vt ch, s tng hp protein, ADN hoc ARN c trng ca t bo, ngay lp tc b virus nh ch gn nh hon ton, v thay vo l qu trnh sinh tng hp cc thnh phn ring ca virus, do virus iu ha c tin hnh. y l giai on phc tp nht ca qu trnh nhn ln ca virus, ph thuc vo loi axit nucleic ca virus v kt qu cui cng l tng hp c axit nucleic v cc thnh phn protein cu trc khc nhau ca virus.

- Virus c axit nucleic l DNA ds + T khun mu DNA ca virus tng hp nn mRNA phc v cho vic tng hp nn enzim DNA polymerase v nguyn liu DNA mi. + T DNA mi c tng hp, mRNA c tng hp to nn protein capsit v cc thnh phn cu trc khc ca virus. - Virus c axit nucleic l RNA mt si dng RNA ca virus ng thi l mRNA tng hp nn RNA polymerase v ARN mi ca virus.

- Virus c axit nucleic l RNA nhng c enzim sao chp ngc Enzyme sao chp ngc l DNA polymerase ph thuc vo ARN hay cn gi l reverse transcriptase (RT). T RNA ca virus tng hp nn DNA trung gian, DNA ny tch hp vo NST ca t bo vt ch. DNA trung gian l khun mu tng hp nn ARN virus v y cng l mRNA tng hp nn cc thnh phn cu trc khc ca virus.

Giai on 4. Giai on lp rp cc thnh phn virus Giai on lp rp cc thnh phn virus ny thng xy ra gn mng t bo, axit nucleic v protein c tng hp cc ni khc nhau trong t bo, chng c chuyn dch li gn nhau v kt hp vi nhau to thnh virus hon chnh. Nh enzyme cu trc ca virus hoc enzim ca t bo cm th gip cho cc thnh phn cu trc mi ca virus c lp rp theo khun mu ca virus gy bnh to thnh nhng virus mi.

Vi virus dng trn (c axit nucleic v capsit): cc phn t protein va chm vi nhau to thnh mt vng cung protein capsit bao quanh axit nucleic. Cng mt lc c hng trm, hng ngn, hng vn virus c lp rp theo kiu ny. Vi virus dng v (c axit nucleic, capsit v v ngoi): cng lp rp ging nh trn, nhng v ngoi ca virus khng phi do sinh tng hp to thnh m l do mng t bo cht ca vt ch b virus bin i to thnh v ca virus.

Giai on 5. Giai on gii phng virus ra khi t bo Sau khi c lp rp hon chnh, hoc cc thnh phn c bn, virus chun b gii phng khi t bo. C 3 cch gii phng virus

Cch gii phng t T bo nhim virus b n tung v virus c gii phng t vi s lng ln, sau tip tc gy nhim t bo lnh. C ch: + Virus c th ph v vch t bo sau vi gi cho ti vi ngy, ty theo chu kz nhn ln ca tng loi virus gii phng hng lot virus ra khi t bo gy nhim v tip tc mt chu kz nhn ln mi trong t bo cm th. + Di tc dng ca enzim, vch t bo b ph v, b tan r hon ton v cc virus t cng lc chui ra khi t bo tip tc xm nhp vo t bo lnh. + Sau qu trnh nhn ln s lng virus sn sinh ra nhiu gy p lc ln vch t bo, v do phi chu mt sc ti qu ln, nn vch t bo b ph v v virus ng lot chui ra khi t bo.

M hnh c ch xm nhim v nhn ln ca virus cm A t bo ch

Cch gii phng t t theo li ny chi Thng xy ra i vi mt s virus c v bc ngoi cng. Trong t bo nhim, cc thnh phn ca virus mi tng hp c chuyn v gn mng t bo v lp rp li dng trn nhng cha c v bc. Mng t bo ti ni b virus cm ng bin i, c bit c gn cc thnh phn protein v ca virus vo. Mng t bo li ra v virus c bc vo, cui cng ton b virus b dt ra khi b mt t bo v virus c gii phng.

Cch gii phng qua cu ni t bo t bo Mt s loi virus cn c th truyn t t bo nhim sang t bo lnh m khng cn chui ra mi trng bn ngoi. Gia t bo b nhim v t bo lnh xut hin nhng cu ni nguyn sinh cht, cc ht virus c th truyn qua cc cu ni ny nh chy trong ng dn m khng chui ra khi t bo.

IV. CC NHM VIRUS GY BNH CHNH PHN LOI

1. Theo vt ch ca virus

2. Theo genom
3. Theo mc gy bnh v tnh cht gy bnh

1. Phn loi heo vt ch ca virus

ng vt Thc vt

Vt ch virus

Vi khun

Nm

2. Phn loi virus theo theo genom

Nhm Nhm 1
Nhm 2 Nhm 3 Nhm 4 Nhm 5 Nhm 6 Parvovirus Reovirus Picornavirus, Togavirus Rabdovirus, Paramyxovirus, Orthomyxovirus, Arenavirus Retrovirus

i din Herpesvirus, Poxvirus, Adenovirus, Papovavirus

Genome DNA
DNA+ RNA RNA+ RNA RNA+ (*)

(*) Nh enzyme phin m ngc chuyn RNA+ thnh DNA

3. Phn loi virus theo mc v tnh cht gy bnh Gm 6 nhm

1). Poxvirus 2). Herpesvirus 3). Adenovirus 4). Myxovirus

5). Arbovirus
6). Picornavirus/ Nanivirus

1) Poxvirus *) c im - Genome l ds DNA - Kch thc ln 300 nm 400nm - Xm nhp vo c th qua tuyn nc bt - Gy tn thng cc vng di da *) i din: virus u ma Variola maior v Variola minor

2) Herpesvirus *) c im - Genome l ds DNA - Kch thc 150 250nm - Cu trc i xng 20 mt - Gy nhng bnh mn rp quanh ming *) i din: Herpes simplex (Herpes hominis), H. varicellacea

3) Adenovirus *) c im - Genome l ss DNA xon - Vt ch: ngi, kh, b, g - Khng ete

4) Myxovirus *) c im - Genome l RNA - Kch thc: 80 150 nm - mn cm vi ete *) i din: Myxovirus newcastb; Myxovirus influenza (H1N1, H2N2), Paramyxovirus, Rhabdovirus

5) Arbovirus (Arthropod born virus) *) c im - Ly sang ngi t cn trng - Kch thc: 15 40 nm - Bnh thng gp: vim no Nht Bn, vim no nga

6) Picornavirus (Nanivirus) *) c im - Genome: RNA - Kch thc: 15 30 nm - Khng mn cm vi ete *) i din: Poliovirus hominis gy bi lit tr em

MT S VIRUS GY BNH THNG GP KHC

- Hepatitis B virus

Chu trnh nhn ln ca Hepatitis virus

- HIV

Cu to ca HIV

Chu kz nhn ln ca HIV

Chu kz nhn ln ca HIV

CC VN C LIN QUAN N VIRUS

*) Viroid v Prion

*) Virus v ung th *) IFN

*) Cc loi thuc chng virus