VIN NGHIN CU V PHT TRIN CNG NGH SINH HC

-----

-----

BO CO VIRUS HC I CNG

VIRUS CM A
(INFLUENZA A VIRUS)

CN B HNG DN

SINH VIN THC HIN

Bi Th Minh Diu

Nguyn Trng Duy Anh 3102719

Phan L Nhn

3102761

Phm Kim Ngn

3102755

on Cng Tht

3102784

Nguyn Thy Linh

3102836

Nguyn Th Hnh Nguyn 3102839

Nguyn H Xuyn

---- ---Cn Th, Thng 10/2012

3102797

Trng HCT

Bo co mn Virus hc i cng

MC LC
MC LC1
DANH SCH HNH...2
T VN ..3
MC LC......................................................................................................................... 1
MC LC1
....................................................................................................................................... 1
DANH SCH HNH...2
....................................................................................................................................... 1
T VN ..3
....................................................................................................................................... 1
DANH SCH HNH.........................................................................................................2
T VN .................................................................................................................... 3
I.S LC V VIRUS CM...................................................................................4
2.Phn loi virus cm......................................................................................... 4
3.Mt s dch cm xy ra trn th gii..........................................................6
a.H5N1............................................................................................................ 7
b.Mt s loi cm A khc: ..............................................................................7

II.VIRUS CM A......................................................................................................8
1.Danh php....................................................................................................... 8
2.Cu to............................................................................................................ 8
a.Lp v.......................................................................................................... 9
b.H gen (Genome)......................................................................................... 9
3.c im v cc phng thc bin i khng nguyn..................................11
a. c im khng nguyn...........................................................................11
b. Cc phng thc bin i khng nguyn..................................................13
4. C ch xm nhim v nhn ln ca virus.....................................................15

Vin NC & PT CNSH

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

5.Kh nng gy bnh....................................................................................... 16

6.Sc khng ............................................................................................... 17

III. BNH CM.......................................................................................................17

4.Triu chng................................................................................................... 17
5.Cch phng nga v iu tr bnh cm........................................................18
a. Cch phng nga...................................................................................... 18
b. iu tr bnh cm..................................................................................... 20

TI LIU THAM KHO.............................................................................................25

DANH SCH HNH

Hnh 1. Mt s hnh nh v virus cm di knh hin vi in t...............................4
Hnh 2. Cu trc virion ca mt virus cm A............................................................8
Hnh 3. Cu trc lp v ca virus cm A..................................................................9
Hnh 4. Cc phn on gen ca virus cm A.............................................................9
Hnh 5. Cu trc khng nguyn HA........................................................................11
Hnh 6. S minh ha t bin im ca hin tng lch khng nguyn(A) v t
bin ti t hp ca hin tng trn khng nguyn(B) virus cm A.................14
Hnh 7. S xm nhim v nhn ln ca virus cm...................................................15
Hnh 8. Mi quan h ly nhim v thch ng cc loi vt ch ca virus cm A......16
Hnh 9. Cc loi thuc khng virus c s dng hin nay.....................................21

Vin NC & PT CNSH

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

T VN
Nhiu nghin cu hin nay a ra mt s nh gi quan trng rng virus c nhiu
c ch xm nhim v gy bnh cho tt c cc loi sinh vt. Cc bnh do virus gy ra
th kh tr hoc khng c thuc tr, v cc bnh c th bng pht thnh i dch trn
ton cu. Cho nn vic nghin cu n tr nn rt cp thit.
Virus c nhn nh l thc th cha c cu to t bo, c kch thc siu hin
vi v c cu to rt n gin, ch gm mt loi acid nucleic, c bao bi v protein,
mt s c mng bao bn ngoi. Virus mang thng tin di truyn trong acid nucleic v
nhn ln nh b my tng hp ca t bo, v th chng k sinh ni bo bt buc.
Virus khng hot ng bn ngoi t bo ch v iu ny khin mt s ngh
rng chng khng sng. Tt c cc loi sinh vt sng bao gm ng vt, thc vt, nm
v vi khun u l k ch cho virus, nhng hu ht cc virus ly nhim ch k sinh
trong mt loi k ch. Virus c kh nng gy bnh mi c th sng t vi khun n
con ngi, l th phm gy ra bit bao cn bnh him ngho m n nay cc nh khoa
hc vn cha tm ra vaccin c tr.
Cm l mt dch bnh c th xut hin bt c lc no v bt c ni u trn ton
th gii, chng bng n vi t hoc khng c cnh bo. S lng ngi b nh hng
c th ln n hng trm nghn ngi, tng thit hi t cc i dch ln n hng triu
USD.
Trong s cc type thuc dng virus cm, type virus cm A gy thit hi nng n
nht vi cc virus ni bt nh virus cm ln H1N1, virus cm gia cm H5N1,
Bi chuyn ny cung cp kin thc tng quan v khi nim ca virus cm A,
cu trc v b gene, chu k sng, s a dng cng nh c ch xm nhim, gy bnh
ca virus cm A nhm hn ch thit hi t cc dch bnh do cc virus ny mang li.

Vin NC & PT CNSH

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

A. NI DUNG
I.

S LC V VIRUS CM
1.

Khi nim

Virus cm (Influenza virus) thuc h Orthomyxoviridae trong h thng phn

loi chung, c b gen RNA - l nguyn nhn gy ra bnh cm.

Hnh 1. Mt s hnh nh v virus cm di knh hin vi in t

2.

Phn loi virus cm

Influenza virus c phn thnh 3 type:

Influenza virus A( virus cm A)

Influenza virus B( virus cm B)

Influenza virus C( virus cm C)

Phn loi chng Virus cm cn c vo s hin din ca cc glycoprotein b mt,

glycoprotein gy ngng kt hng cu Hemagglutinin (HA) v men tan nhy

Neuraminidase (NA) ( Hemagglutinin v Neuraminidase c gi l cc yu t khng
nguyn ca virus).
Cc chng virus cm A v virus cm B bao gm cc nhm khc nhau. Cc yu t
HA v NA do cc gen quy nh nn khi cc gen bin i, nhng yu t khng nguyn
ny bin i theo. C hai loi bin i mc phn t:

Cc t bin im (point mutations): Thng xy ra trn hai gen m ha cc

thnh phn khng nguyn dn n cc bin i nh ca HA v NA (ngi ta
dng thut ng bin i tri dt (antigenic drift) m t cc t bin kiu ny).
Kt qu hnh thnh nhiu kiu khng nguyn HA v NA khc nhau c ghi
nhn bng cc k hiu H1, H2, H3 v.v. v N1, N2, N3, v.v. V vy k hiu
mi loi virus ta dng mt nhm gm hai k hiu mt t H v mt t N nh:

Vin NC & PT CNSH

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

H1N1, H1N2, H2N2, H5N1, iu ng lu l kt qu ca bin i tri dt

dn n s ra i ca chng virus cm mi m khng th i vi cc chng virus
trc n khng nhn ra c.

Cc bin i ln c tnh chuyn i (antigenic shift): xy ra khi virus cm nhim

t loi ny sang loi khc hoc do trn ln, ti t hp gen ca virus cm cc
loi khc nhau (v d gia virus cm A ngi v virus cm A gia cm). Khi
loi bin i ny xy ra s cho ra i mt phn chng virus mi m tc hi ca n
kh th lng trc c. y l mt trong nhng yu t mt i dch bng
pht.

Chng virus cm nhm A: c chia thnh cc phn nhm da vo t hp cc

khng nguyn (HA) v cc khng nguyn (NA). Tt c c 16 loi protein H, i vi

mi loi th li c n 9 phn nhm protein N, khi t hp li th c kh nng to ra 144
phn nhm virus cm chng A khc nhau. Cc loi chim hoang d, gia cm, ln, nga,
mt s ng vt khc v ngi c th tr thnh vt ch ca tt c cc phn chi ca
virus cm A. Mt s chng virus cm nhm A c xc nh nhim c ngi v
gia cm bao gm:
Cm A H5: Gm 5 phn nhm c xc inh, trong nhm c c lc cao
H5N1 v ang lu hnh ti chu v chu u.
Cm A H7: Gm 9 phn nhm c xc inh. H7 c th nhim t cc loi
chim hay gia cm mang virus sang ngi. Ngi b nhim cc virus H7 c th
biu hin triu chng t vim kt mc mt hay cc triu chng tn thng
ng h hp trn hoc c hai. c bit, H7 hin din trong c nhm c c lc
thp v nhm c c lc cao. Nhn chung, H7 c th gy bnh cho ngi t
biu hin cc triu chng dng nh cho n t vong.
Cm A H9: Gm 9 phn nhm c th nhim ngi (t xy ra v c c lc
thp).

Chng virus cm nhm B: Thng ch pht hin thy ngi nhng t gy

thnh dch nh virus cm A.

Chng virus cm nhm C: Ngi b nhim virus cm C c th biu hin cc

triu chng dng nh. Virus cm C khng gy thnh dch.

Vin NC & PT CNSH

Lp Cng ngh sinh hc K36

Trng HCT

3.

Mt s dch cm xy ra trn th gii

a.

Bo co mn Virus hc i cng

H1N1

Cm H1N1: chng virus cm A c phn lp u tin, nguyn nhn ca hu ht

cc bnh cm ngi. L bnh nhim trng ng h hp cp tnh do vi rt cm
H1N1 gy nn. Bnh c kh nng ly nhim rt cao v ly lan nhanh trong cng
ng. T chc Y t th gii cnh bo dch cp 6, cp cao nht v l
i dch trn quy m ton cu.

Thng su nm 2009, T chc Y t th gii thng bo mt bin th mi ca

H1N1 c ngun gc t ln l nguyn nhn ca dch cm nm 2009. Bin th ny
thng c truyn thng i chng gi l "cm heo" hoc "cm ln".

Vi-rt cm H1N1 tn ti kh lu ngoi mi trng, c th sng t 24 n 48 gi

trn cc b mt nh bn, gh, t, tay vn cu thang...; tn ti trong qun o t 8
n 12 gi v duy tr c 5 pht trong lng bn tay.

Bnh ly truyn t ngi sang ngi theo ng h hp, qua cc git nc bt hay
dch tit mi hng khi ngi bnh ho, ht hi, hoc ly qua tip xc vi mt s
vt c cha vi rt ri qua bn tay a ln mt, mi, ming. Ngi mang vi rt
cm H1N1 c kh nng truyn vi rt cho nhng ngi xung quanh trong thi
gian 1 ngy trc ti 7 ngy sau, k t khi c triu chng ca bnh. Bnh ly lan
cng mnh, cng nhanh khi c s tip xc trc tip vi ngi bnh, c bit ni
tp trung ng ngi nh trng hc, nh tr... Hin nay cha c vc xin c
hiu phng chng cm H1N1. Khi c vc xin, vic tim phng bnh phi tun th
theo hng dn ca c quan y t.

Cc du hiu chnh khi nhim cm H1N1: Bnh c biu hin st trn 38 C, ho,
au hng, s mi, au u, au c, mt mi. Mt s trng hp nng c th b
suy h hp v dn n t vong.

n nay, dch cm H1N1 chnh thc ly lan trong cng ng. Vit Nam c
763 trng hp nhim cm H1N1, trong khu vc pha Nam c 680 ca, s ca
bnh tp trung i tng t 10 n 29 tui.

Vin NC & PT CNSH

Lp Cng ngh sinh hc K36

Trng HCT

a.
-

Bo co mn Virus hc i cng

H5N1

H5N1 l mt phn nhm c kh nng gy nhim cao ca virus cm gia cm.

Chng virus ny ln u tin c pht hin xm nhim trn ngi ti Hng
Kng nm 1997.

Chnh nhm virus cng l tc nhn gy dch cm trn gia cm Hng Kng lc
. Tn gi phn nhm H5N1 l lin quan n loi protein khng nguyn trn v
virus: protein hemagglutinin nhm 5 (H5) v neuraminidase nhm 1 (N1).

ng ly nhim: Cc chng ca virus cm g c th xm nhim vo nhiu loi

ng vt khc nhau nh chim, ln, nga, hi cu, c voi v con ngi. Bnh cm
g ly truyn qua khng kh v phn bn, nhng cng c th gy nhim trn thc
n, nc, dng c v qun o. Tuy nhin, hin gi cha c bng chng thc
nghim no cho thy virus cm g c th sng st trong thc n c nu
chn.

Thi k bnh t 3 n 5 ngy. Triu chng mc bnh cc ng vt l khc

nhau, nhng mt s bin th virus c th dn n t vong ch trong vng vi
ngy.

Triu chng ngi: cm g gy ra cc triu chng tng t nh ca cc loi cm

khc. l st, ho, au hng, au nhc c bp, vim mng kt v nhng
trng hp nghim trng, c th gy suy gim h hp v vim phi, c th dn
n t vong. Mc nghim trng ca bnh ph thuc phn ln vo th trng
sc kho, kh nng min dch, tin s tip xc virus ca ngi b nhim.

Tnh n ngy 28 thng 2, 2008, trn th gii c 369 trng hp ngi nhim
virus H5N1 v trong 234 ngi t vong. Quc gia chu tn tht v ngi
nng n nht l Indonesia v Vit Nam. c 10 quc gia chu v chu u
pht hin thy virus H5N1. Ngoi ra, hn 120 triu con chim (gia cm) b cht
do nhim virus hoc b tiu hu.
b.

Mt s loi cm A khc:

H2N2: gy nn dch cm chu vo nm 1957 v 1958 lm cht khong 1

triu ngi trn th gii.

Vin NC & PT CNSH

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

H3N2: c pht trin t chng H2N2 do bin i di truyn v gy nn dch cm

Hng Kng vo nm 1968, 1969 gy t vong 750.000 ngi. y l i dch
gy t vong ln nht th k 20.

H7N2: bng pht trong gia cm vo nm 2002, 44 ngi c pht hin l b

nhim virus ti bang Virginia, Hoa K.

II.

VIRUS CM A
1.

Danh php

Chng virus cm A c phn thnh cc phn type (subtype), cc phn type ny

c phn bit bi s khc nhau cc c tnh khng nguyn b mt (NA v HA), cho
p ng min dch khc nhau gia cc chng virus c th b nhim. n nay pht
hin c 17 phn type HA (H1 H17) v 9 phn type NA (N1 N9) nhng virus gy
bnh ngi thng thy cc phn type H1, H2, H3 v N1, N2.
T chc Y t th gii (WHO) quy nh thng nht danh php theo th t k
hiu: Virus type - Loi ng vt b nhim - Vng a l phn lp - S hiu ng k
chng virus - Nm phn lp virus subtype( i vi cc virus c phn lp trn
ngi bnh, th khng cn ghi loi b nhim trong danh php).
2.

Cu to

Hnh 2. Cu trc virion ca mt virus cm A

Virus cm A thng c hnh cu, c ng knh t 80 120nm, khi lng phn
t khong 250 triu Da. Phn tch thnh phn ha hc mt virion c cha khong 0,8 1,1% RNA; 70-75% protein; 20 - 24% lipid v 5 - 8% l carbonhydrate. Ht virus c

Vin NC & PT CNSH

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

cu to gm v (capsid), v bc ngoi (envelope) v li l RNA si n m (negative

single strand).
a.

Lp v

V virus c chc nng bao bc v bo v vt cht di truyn RNA ca virus. Bn

cht cu to ca v l mng lipid kp, c ngun gc t mng t bo vt ch v c gn
thm nhng protein c bn cht khng nguyn l HA, NA v cc knh ion (ion
channel) M2. Bn trong lp lipid ny l mt khung sn protein nn M1 (Matrix
protein)

Hnh 3. Cu trc lp v ca virus cm A

b.

H gen (Genome)

Vt cht di truyn ca virus cm A l RNA si n m (vit tt l (-) ssRNA).

Gm 8 phn on gen ring bit mang tn t 1-8 theo th t gim dn ca kch thc
phn t (hay c gi theo tn protein m chng m ha tng hp), m ha cho 11
protein khc nhau ca virus gm: HA, NA, M (M1 v M2), NP, NS (NS1 v NS2),
PA, PB1 v PB2.

Hnh 4. Cc phn on gen ca virus cm A

Vin NC & PT CNSH

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

Phn on 1 (gen PB2): m ha tng hp protein enzyme PB2, l tiu n v

thnh phn trong phc hp enzyme polymerase ca virus, chu trch nhim
khi u phin m RNA virus.
Phn on 2 (gen PB1): m ha tng hp enzyme PB1 v PB1-F2. PB1 l tiu
n v xc tc ca phc hp enzym polymerase trong qu trnh tng hp RNA
virus, chu trch nhim gn m RNA. PB1-F2 c m ha bi mt khung c
m khc ca PB1, c vai tr gy ra hin tng apoptosis( hin tng t bo
cht theo chng trnh).
Phn on 3 (gen PA): m ha tng hp protein enzyme PA. PA l mt tiu
n v ca polymerase chu trch nhim ko di s phin m RNA trong qu
trnh tng hp RNA ca virus.
Phn on 4 (gen HA): l mt gen khng nguyn ca virus, l gen chu trch
nhim m ha tng hp protein HA - khng nguyn b mt virus cm.
Phn on 5 (gen NP): m ha tng hp nucleoprotein (NP) l thnh phn ca
phc h phin m, chu trch nhim vn chuyn RNA gia nhn v t bo cht
ca t bo ch.
Phn on 6 (gen NA): l mt gen khng nguyn ca virus, l gen chu trch
nhim m ha tng hp protein NA - khng nguyn b mt capsid ca virus.
Phn on 7 (gen M): m ha cho protein m (matrix protein - M) ca virus
(gm hai tiu phn l M1 v M2).
Phn on 8 (gen NS): l gen m ha protein khng cu trc (non structural

protein), m ha tng hp hai protein l NS1 v NS2 (cn gi l NEP, nuclear

export protein), c vai tr bo v h gen ca virus nu thiu chng virus sinh ra
s b thiu nng.
Mi phn on RNA ca virus cm A c cu trc xon bc 2 i xng di 50 100nm, ng knh 9 - 10nm, c bao bc bi nucleoprotein (NP) - bn cht l
lipoprotein, to thnh cu trc ribonucleoprotein (RNP). Mi cu trc RNP li kt hp
vi 3 protein enzyme polymerase (PA, PB1 v PB2) - chu trch nhim trong qu trnh
phin m v sao chp RNA ca virus.

Vin NC & PT CNSH

10

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

Cc phn on ca h gen virus cm A ni vi nhau bng cc cu ni peptide to

nn vm (loop) ti gii hn cui ca mi phn on, v to thnh mt si RNA duy
nht c tng di t 10.000 - 15.000 bp (tu theo tng chng virus cm A).
H gen virus cm A khng c gen m ha enzyme sa cha RNA.
3.

c im v cc phng thc bin i khng nguyn

a. c im khng nguyn

Khng nguyn HA (hemagglutinin)

Hnh 5. Cu trc khng nguyn HA

Khng nguyn HA l mt glycoprotein thuc protein mng type I (lectin), c
kh nng gy ngng kt hng cu g trong ng nghim (invitro). Khng nguyn HA
c m ha bi phn on 4 ca h gen virus cm A, c c tnh kt hp vi th th
c hiu trn b mt mng ca t bo nhim. C 17 type HA (H1 H17) c pht
hin nhng ch c 3 type l H1, H2, H3 gy bnh cho ngi.
Phn t HA c dng hnh tr, di khong 130A 0, cu to gm 3 n phn
(trimer), mi n phn (monomer) c to thnh t hai tiu n v HA 1 (36 kDa) v
HA2 (27 kDa), lin kt vi nhau bi cc cu ni disulfide (-S-S-). Cc n phn sau
khi tng hp c glycosyl ha (glycosylation) v gn vo mt ngoi capsid l tiu
n v HA2, phn u t do hnh chm cu c to bi tiu n v HA 1 cha ng v
tr gn vi th th thch hp ca HA trn b mt mng t bo ch (Hnh 7).
C khong 400 phn t HA trn b mt ca mt virus, c vai tr quan trng trong
qu trnh nhn din virus v khi ng qu trnh xm nhim ca virus vo t bo ch.
HA lin kt vi th th c hiu (glycoprotein cha sialic acid) trn b mt mng t
Vin NC & PT CNSH

11

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

bo nhim, khi u qu trnh xm nhim ca virus trn vt ch gip cho virus xm

nhp, ha mng v gii phng RNA h gen thc hin qu trnh nhn ln trong t bo
cm nhim. Qu trnh kt hp ph thuc vo s ph hp cu hnh khng gian ca th
th cha acid sialic ca t bo ch vi v tr gn vi th th ny trn phn t HA ca
virus cm, quyt nh s xm nhim d dng ca virus cc loi vt ch khc nhau.
Protein HA cn l khng nguyn b mt quan trng ca virus cm A, kch thch
c th sinh ra p ng min dch dch th c hiu vi tng type HA, v tham gia vo
phn ng trung ha virus, c coi l protein va quyt nh tnh khng nguyn, va
quyt nh c lc ca virus.

Khng nguyn NA(neurominidase)

Khng nguyn NA (cn gi l sialidase) l mt protein enzyme c bn cht l

glycoprotein c gn trn b mt capsid ca virus cm A, mang tnh khng nguyn

c trng theo tng phn type NA. C 9 phn type NA (N1 - N9) c pht hin ch
yu virus cm gia cm, hai phn type N1 v N2 c tm thy virus cm ngi.
C khong 100 phn t NA xen gia cc phn t HA trn b mt capsid ht
virus. Phn t NA c dng nt li hnh nm, u t do (cha vng hot ng) gm 4
di n v ging nh hnh cu nm trn cng mt mt phng, v phn k nc gn
vo v capsid.
Protein NA c vai tr l mt enzyme ct t lin kt gia gc sialic acid ca
mng t bo nhim vi phn t cacbonhydrate ca protein HA, gii phng ht virus ra
khi mng t bo nhim, y nhanh s ly nhim ca virus trong c th vt ch, v
ngn cn s tp hp ca cc ht virus mi trn mng t bo. Mt khc, NA cn tham
gia vo phn ct lin kt ny trong giai on ha mng, y nhanh qu trnh ci o
(uncoating) gii phng h gen ca virus vo trong t bo cht ca t bo nhim, gip
cho qu trnh nhn ln ca virus din ra nhanh hn.
NA cn phn ct cc lin kt glycoside, gii phng neuraminic acid lm tan
long mng nhy b mt biu m ng h hp, to iu kin cho virus nhanh chng
tip cn t bo biu m v thot khi cc cht c ch khng c hiu.
Ngoi ra, NA cn l mt khng nguyn b mt ca virus, tham gia kch thch h
thng min dch ca c th ch, sinh ra khng th c hiu vi khng nguyn NA ca
cc chng virus ng nhim c tc dng phong ta protein NA.

Vin NC & PT CNSH

12

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

b. Cc phng thc bin i khng nguyn

Hin tng lch khng nguyn
Lch khng nguyn (antigenic drift) thc cht l cc t bin im xy ra cc
phn on gen hay h gen ca virus. Nguyn nhn l do virus cm A k sinh ni bo
bt buc, khng c c ch c v sa bn sao (proof reading) trong qu trnh phin m
v sao chp nhn t bo ch. Tu thuc v tr xy ra cc t bin trong b ba m
ha, m c th trc tip lm thay i cc amino acid trong trnh t ca protein, dn n
thay i thuc tnh ca protein, hoc c tch ly trong phn on gen xy ra t
bin. Tn sut xy ra t bin im rt cao, c mi 10.000 nucleotide th c 1
nucleotide sai khc. Nh vy, gn nh mi ht virus mi c sinh ra u cha ng
mt t bin im trong h gen ca n, v cc t bin ny c tch ly qua nhiu th
h virus s lm xut hin mt phn type virus mi c nhng c tnh khng nguyn
mi c th b sai lch. Hin tng ny thng xy ra cc phn on gen khng
nguyn NA v HA, to ra cc b m tng hp cc amino acid mi, hoc lm thay i
cu trc dn n thay i c tnh ca protein , hoc c kh nng glycosyl ha rt
cao trong cu trc chui polypeptide khng nguyn, to ra mt bin th virus mi thay
i c lc gy bnh hay c tnh khng nguyn mi.
Hin tng trn khng nguyn
Hin tng trn khng nguyn (cn gi l trao i hay ti t hp) cc gen
khng nguyn (antigenic shift) ch c virus cm, v rt t mt s virus RNA gy
bnh gia cm khc, cho php virus c kh nng bin chng rt cao. H gen gm 8 phn
on gen ring bit ca virus cm A c 2 chng virus cm A khc nhau khi ng
nhim trong mt t bo trao i cho nhau, c th xy ra s ho trn (reassort) hoc
trao i (swap) cc phn on gen ca hai chng virus trong qu trnh kt hp li
RNA h gen, to ra cc trng thi khc nhau ca RNA h gen ca cc ht virus mi t
hai RNA h gen ca nhng virus ban u. Kt qu l to ra th h virus mi c cc
phn on gen kt hp, v i khi gip cho chng c kh nng ly nhim loi vt
ch mi hoc gia tng c lc gy bnh.
Vin NC & PT CNSH

13

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

Hnh 6. S minh ha t bin im ca hin tng lch khng nguyn(A) v t

bin ti t hp ca hin tng trn khng nguyn(B) virus cm A.
Hin tng glycosyl ha
Glycosyl ha (glycosylation) l s gn kt ca mt chui carbonhydrate
(oligosaccharide) vo vi amino acid Asparagine (N) mt s v tr nht nh trong
chui polypeptide HA hay NA lm thay i biu hin c tnh khng nguyn ca HA
v NA, gip cho virus thot khi tc ng min dch bo h ca c th ch v iu ho
s nhn ln ca virus.

Vin NC & PT CNSH

14

Lp Cng ngh sinh hc K36

Trng HCT

4.

Bo co mn Virus hc i cng

C ch xm nhim v nhn ln ca virus

Hnh 7. S xm nhim v nhn ln ca virus cm

Virus cm A xm nhp vo t bo ch bng cch to cc cu ni gia cc HA
vi th th c hiu (glycoprotein hoc glycolipid c gn sialic acid) trn b mt ca
mng t bo. Sau khi gn kt vo t bo nhim, virus c a vo bn trong t bo
theo c ch ni bo (endocytosis). Trong mi trng acid ca endosome, hot tnh ca
knh ion M2 c gia tng cho cc H+ trn vo bn trong, dn n pH thp. y l
iu kin rt cn thit virus thay i hnh dng v ha mng envelop ca mnh vi
mng ca endosome (endosomal membrane), ng thi to ra tn hiu gii phng
RNP (ribonucleoprotein) vo t bo cht ca vt ch. T y, RNP c vn chuyn
vo trong nhn ca t bo ch.
Tip theo th phc hp polymerase ca t bo ch gn vo RNA ca virus, tng
hp nn si dng RNA t si khun l si m RNA ca h gen virus. Sau , u
5 ca nhng si dng ny mi gn m 5 methylguanosine (c tch t mRNA ca
t bo cap natch) v c enzyme PB2 gn thm 10 - 12 Adenine, ri vn chuyn
n t bo cht tin hnh qu trnh dch m ti h thng mng ni cht sn tng
hp nn cc protein ca virus.
Vin NC & PT CNSH

15

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

Cc phn t HA v NA ca virus sau khi tng hp c vn chuyn gn ln

mt ngoi ca mng t bo nhim nh b my Golgi, hin tng ny c gi l hin
tng ny chi (budding) ca virus. NP sau khi tng hp c vn chuyn tr li
nhn t bo kt hp vi RNA thnh RNP ca virus. Sau cng cc RNP ca virus
c hp nht vi vng ny chi, to thnh cc chi virus gn cht vo mng t
bo ch bi lin kt gia HA vi th th cha sialic acid. Cc NA phn ct cc lin kt
ny v gii phng cc ht virus trng thnh tip tc xm nhim cc t bo khc.
5.

Kh nng gy bnh

Kh nng gy bnh ca virus cm A ph thuc vo:

c lc: tnh gy bnh hay c lc ca virus cm A c chia lm hai loi:
Loi c lc cao( HPAI - Highly pathogenic avian influenza ): kh nng gy tn

thng nhiu c quan ni tng trong c th nhim( trn gia cm chng thng
gy cht 100% s gia cm b nhim trong vng 48h sau nhim). Loi ny rt
nguy him gy lo ngi cho cng ng.
Loi c lc thp( LPAI - Low pathogenic avian influenza): ch c th gy
bnh cm nh, khng c triu chng lm sng in hnh v khng lm cht vt
ch. y l loi virus ly truyn rng ri v to nn cc bnh trong t nhin
ca virus cm A, loi ny c th trao i gen vi cc chng virus c c lc cao
ng nhim trn cng mt t bo, v tr thnh loi virus HPAI nguy him
Tnh thch nghi vt ch ca tng chng virus: Thng thng chng khng gy
bnh hoc ch gy bnh nh gii hn ng h hp ca chim hoang d v gia
cm nhim, nhng mt s chng c (H5, H7, v H1, H2, H3) c th gy bnh
nng hu ht cc c quan trong c th, gy nn dch cm gia cm v ngi.

Vin NC & PT CNSH

16

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

Hnh 8. Mi quan h ly nhim v thch ng cc loi vt ch ca virus cm A

6.

Sc khng

Virus cm A tng i nhy cm vi cc tc nhn bt hot vt l hay ha hc.

Cc ht virus tn ti thch hp trong khong pH t 6,5 n 7,9. pH qu acid hay qu
kim, kh nng ly nhim ca virus b gim mnh.
Lp v ngoi ca virus bn cht l lp lipid kp, c ngun gc t mng t bo
nhim, d b ph hy bi cc dung mi ha tan lipid, cht ty ra v cc cht st trng:
formaldehyde, phenol, -propiolacton, sodium hypochloride, acid long v
hydroxylamine.
Virus b bt hot di nh sng trc tip sau 40gi, tn ti c 15ngy trong
iu kin nh sng thng, tia t ngoi bt hot c virus nhng khng ph hy c
khng nguyn ca virus.
Tn ti t nht 3 thng nhit thp (trong phn gia cm), v ti hng nm
nhit bo qun (70oC). Trong ph tng gia cm (40oC), virus tn ti 25 - 30 ngy,
nhng ch tn ti 7 - 8 ngy nhit c th ngi (37 oC); trong nc, virus c th
sng ti 4 ngy nhit 30 oC. Tuy nhin, virus cm A d dng b tiu dit hon ton
100oC v 60oC trong 30 pht.
III. BNH CM
4.

Triu chng

Cc triu chng ca bnh cm thng bao gm:

St: Ngi b cm thng b st t 2-5 ngy v t ht sau 24 n 48 gi.

Vin NC & PT CNSH

17

Lp Cng ngh sinh hc K36

Trng HCT
-

Bo co mn Virus hc i cng

Nhc u v au nhc bp tht: Hu ht nhng ngi b cm c biu hin au

nhc bp tht, v mt s ngi cng c triu chng ging nh cm lnh (chy
nc mi, au hng). Cc triu chng ca cm thng ci thin trong 2-5 ngy,
mc d bnh c th ko di trong mt tun hoc hn.

Mt mi: c th ko di trong vi tun.

Cc biu hin bin chng ca bnh cm:

Cm thy kh th, bi ri.

au hoc c cm gic nng trong lng ngc hoc d dy.

Nn ma, c du hiu mt nc, chng mt,..

tr nh: + Da v ti xanh hay ta

+ Khng c nc mt khi khc ( tr s sinh)
+ B st pht ban
+ Khng thc dy c.

Nhm ngi c nguy c bin chng cm cao: ph n mang thai, tr nh di 5

tui( c bit l di 2 tui), ngi gi trn 65 tui v nhng ngi c bnh phi
mn tnh, bnh tim, tiu ng , h min dch km( nhim HIV hoc cy ghp
tng) v mt s bnh khc. Cc bin chng ca cm c th dn n vim phi mt bnh nhim trng nghim trng ca phi.

Nu thy xut hin cc biu hin ca bin chng cm nn n gp ngay bc s

tin hnh iu tr kp thi.
5.

Cch phng nga v iu tr bnh cm

a.

Cch phng nga

Cch hiu qu nht phng nga cm l tim nga cm v s dng cc bin

php kim sot ly nhim n gin.

Chng vaccine nga cm: Chng nga cm l cch hiu qu nht gim
nguy c b nhim cm. Nhng ngi c chng thuc nga cm c nguy c
ly nhim v t l t vong do cm thp hn so vi nhng ngi khng c
chng nga.
Thi gian chng nga: Bi v virus cm thng bin i theo tng nm nn
cn mt loi vaccine cm mi trc khi mi t cm. Nn chng nga cm

Vin NC & PT CNSH

18

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

cng sm cng tt c c hiu qu tt nht. Bc bn cu, ma cm

thng xy ra gia thng mi mt v thng t. Nam bn cu, ma cm
thng xy ra gia thng nm v thng mi. Bnh cm c th xy ra ti bt k
thi gian no ca nm vng nhit i.
Hiu qu ca vaccine: Khi c tim c chng khng th (protein), c th
s tiu dit cc virus cm sau khi tip xc. Thng mt khong hai tun to
ra cc khng th. Vaccine c th bo v t 50 n 80% nhng ngi c
chng nga. Nu b nhim cm sau khi c chng nga, cc triu chng ca
c th s nh hn v khi trong mt thi gian ngn hn.
Cc hnh thc chng nga: C 3 hnh thc chng nga ph bin hin nay:
Tim vo c: ngi ln v tr em 6 thng tui tr ln
Tim vo da: s dng kim tim nh v vaccine t hn nhng hiu qu cng
tng ng vi tim nga cm thng thng. Cch ny ch dng cho
ngi ln t 18 n 64 tui.
Xt mi: ch dnh cho tr em khe mnh t 2 nm tui tr ln v ngi ln
khe mnh khng qu 49 tui. Ph n mang thai v nhng ngi c h min
dch yu hoc ngi c bnh mn tnh khng nn xt mi v n c cha
virus sng.

Tc dng ph ca vaccine: Cc tc dng ph thng gp nht ca tim nga

bnh cm l au ti ch tim. Nhng tc dng ph c th c ca cc vaccine bao
gm au nhc c th, au u v st nh. Nhng vn ny thng t nghim
trng v bin mt trong vng mt hoc hai ngy. C nhiu s lo ngi v an ton
ca vaccine, vaccine khng an ton 100% cho tt c mi i tng. Tuy nhin,
nguy c bin chng do thuc chng nga l rt nh.

Thuc khng virus: thuc khng virus c th gip lm gim nguy c pht trin
bnh cm sau khi tip xc vi ngi b nhim. Nhng loi thuc ny cng c th
c s dng cho nhng ngi c nguy c b bin chng t bnh cm v nhng
ngi khng th tip nhn vaccine cm.

Kim sot nhim khun:

Vin NC & PT CNSH

19

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

Ra tay thng xuyn vi x phng v nc c th gip hn ch s ly lan ca

cm. C th dng cht kh trng tay c cha cn. Ngi ang b nhim cm
hoc ngi chm sc cho bnh nhn cm u cn phi ra tay thng xuyn.
Che ming v mi khi ho hoc ht hi v ra tay ngay lp tc. Khng nn ht
hi hoc ho vo tay o v nhng ni khc trn qun o y c th tr thnh ni
chanc bt v cc dch tit khng gy nhim bn tay.
Hn ch chm tay bn vo mt, mi v ming v y l con ng ly lan ca
virus.
Trnh tip xc gn gi vi ngi b bnh.
Khi mc bnh, hn ch tip xc vi nhng ngi khc trnh ly nhim cho
h.
b.

iu tr bnh cm

Hu ht nhng ngi b cm phc hi trong vng 1-2 tun m khng cn iu

tr. Tuy nhin, cc bin chng nghim trng ca bnh cm c th xy ra. Khi cn
phi tin hnh iu tr theo cc cch sau:
iu tr triu chng
S dng cc dc phm cha Acetaminophen v Aspirin c th lm gim st,
nhc u v au c. (Aspirin khng nn dng cho tr em di 18 tui v aspirin
c th dn n mt cn bnh nghim trng gi l hi chng Reye). Cc loi
thuc ho thng khng hu ch, ho thng t khi m khng cn iu tr. Cc
dc phm phi c s dng theo hng dn ca bc s.
iu tr cc triu chng ca cm c th gip bnh bt i cc biu hin st, au
u, au c,... Nhng cch ny s khng lm cho bnh mau khi hn.
Bnh nhn cn c ngh ngi cho n khi bnh cm hon ton khi, c bit
l khi bnh nghim trng.
Ung nhiu nc, khng b mt nc.
iu tr khng virus
Thuc khng virus c th c s dng iu tr hoc phng nga cm. Khi
c s dng nh mt bin php iu tr, thuc khng loi b cc triu chng
cm, mc d n c th lm gim mc nghim trng v thi gian ca cc
Vin NC & PT CNSH

20

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

triu chng khong mt ngy. Ty theo tng trng hp m a ra quyt nh

c s dng thuc khng virus iu tr hay khng. Nhng trng hp ch b
bnh nh v khng c yu t nguy c bin chng thng c iu tr bng
mt loi thuc khng virus nu cc triu chng xut hin trong vng 48 gi
hoc t hn, khng c iu tr nu cc triu chng qu 48 gi.
Cc thuc khng virus c s dng iu tr hoc phng nga bnh cm l
oseltamivir (Tamiflu ) v zanamivir (Relenza ). Hai loi thuc khng virus
khc l rimantadine (Flumadine ) v Amantadine (Symmetrel ), tng c
s dng trc y gi khng cn hiu qu v b hu ht cc virus cm khng
li. Thuc khng virus iu tr hiu qu nht cho cm theo ma khi n c s
dng trong vng 48 gi u tin ca triu chng cm.
Tc dng ph : Zanamivir v oseltamivir c th gy ra tc dng ph nh, bao
gm bun nn v i ma, zanamivir c th gy ra kh th trong mt s trng
hp. Hu ht bnh nhn vn c th tip tc dng thuc mc d c cc tc dng
ph.

Vin NC & PT CNSH

21

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

Hnh 9. Cc loi thuc khng virus c s dng hin nay

S dng khng sinh: Khng sinh rt hu ch cho vic iu tr cc bnh do virus
nh cm. Thuc khng sinh ch nn s dng nu c vi khun l mt bin chng ca
cm nh vim phi do vi khun, nhim trng tai, hoc vim xoang. Thuc khng
sinh c th gy ra tc dng ph v dn n pht trin khng khng sinh.
Ngoi ra cn c cc phng php iu tr b sung v thay th khc ang c
nghin cu v nh v an ton ca chng.

Vin NC & PT CNSH

22

Lp Cng ngh sinh hc K36

Trng HCT

Vin NC & PT CNSH

Bo co mn Virus hc i cng

23

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

B. KT LUN
Chng virus cm nhm A c chia thnh cc phn nhm da vo t hp cc
khng nguyn (HA) v cc khng nguyn (NA). Tt c c 16 loi protein H, i vi
mi loi th li c n 9 phn nhm protein N, khi t hp li th c kh nng to ra 144
phn nhm virus cm chng A khc nhau. Gy bnh trn chim hoang d, gia cm, vt
nui v ngi. Cu to gm: lp v mng lipid kp c khng nguyn HA, NA v h
gen l ARN si m. Kh nng gy bnh ca virus cm A ph thuc vo:c lc gm 2
loi c lc cao, c lc thp; tnh thch nghi vt ch ca tng chng virus. Virus
cm A tng i nhy cm vi cc tc nhn bt hot vt l hay ha hc. Cc ht virus
tn ti thch hp trong khong pH t 6,5 n 7,9. pH qu acid hay qu kim, kh
nng ly nhim ca virus b gim mnh. B bt hot di nh sng trc tip sau 40 gi,
tn ti trn 3 thng nhit thp. B tiu dit nhit 1000C.
Bnh cm gm cc triu chng: st, nhc u, au cc bp tht, mt mi,...c
th dn n cc bin chng. Nhm ngi c nguy c bin chng cm cao: ph n
mang thai, tr nh di 5 tui( c bit l di 2 tui), ngi gi trn 65 tui v
nhng ngi c bnh phi mn tnh, bnh tim, tiu ng , h min dch km( nhim
HIV hoc cy ghp tng) v mt s bnh khc. Phng nga bnh cm hiu qu nht l
tim nga v kim sot ly nhim. iu tr bnh cm theo cc cch: iu tr triu
chng, iu tr khng virus, s dng khng sinh.
Do tnh cht nguy him, kh nng ly lan v bc pht thnh dch cao gy nh
hng n sc khe, kh nng lao ng, gy thit hi ln cho nn kinh t nn vic
nghin cu virus cm ni chung v virus cm A ni ring l ht sc cp bch v cn
c chin lc pht trin c th: y mnh nghin cu, kp thi pht hin nhng bin
th mi, c ch xm nhim, vt ch, cch thc ly truyn, c lc ca virus cm t
nghin cu vaccine v a vo sn xut m bo kh nng phng dch. Ch
ng phng nga bng cch tim phng vaccine, nu dch xy ra phi cch ly ngi
bnh, vng dch, i vi vt nui nhim phi tiu hy, hn ch ly lan, tin hnh
kh trng vng dch. Tuyn truyn nng cao thc ca tng c nhn, h chn nui,
cng ng v s nguy him ca virus cm t ch ng trong phng nga.

Vin NC & PT CNSH

24

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

TI LIU THAM KHO

Ting Vit

Nguyn Chung Chnh (2010), ng dng k thut di truyn ngc to virus cm

A/H5N1 Vit Nam gim c lc, lun vn thc s-chuyn ngnh di truyn, trng
i hc Khoa hc T nhin TP.HCM.
Nguyn Tin Dng (2008), Vi nt v virut cm gia cm H5N1, Tp ch Khoa
hc K thut Th y, XV(4), tr. 80-86.
Tp ch KH,CN&MT s 3 nm 2009

Ting Anh

Adwan, G.M. (2009), Highly pathogenic influenza a virus (H5N1) Microbiology,

Medical Journal of Islamic World Acedemy of Sciences, 17(1), pp. 5-16.
Bouvier, N. M., Palese, P. (2008), The biology of influenza viruses. Vaccine, 26S,
D49-D53.
Debi, P. N, Hui, E. K. W., Barman, S., et al. (2004), Assembly and budding of
influenza virus, Virus Research, 106, pp. 147-165
Han, X, Steinhauer, D. A., Wharton, S. A. And Tamm, L. K. (1999), Interaction of
Mutant Influenza Virus Hemagglutinin Fusion Peptides with Lipid Bilayers:
Probing the Role of Hydrophobic Residue Size in the Central Region of the
Fusion Peptide, Biochemistry, 38, pp. 15052-15059.
John B. Carter and Venetia A. Saunders, Virology : principles and applications,
School of Biomolecular Sciences, Liverpool John Moores University, UK.
Copyright 2007 John Wiley & Sons Ltd.
Liu, J. P. (2005), Avian Influenza-A pandemic wating to happen? Microbiol
Immunol Infect, 39, pp. 4-10.
Nippon Rinsho, 1997 Oct. Infulenza virus genome structure and encode pro-teins, J
Med Biol Res, 55(10): 2542-6.
Pan, Y. S,. Wei, H. J., Chang, C. C., et al (2010), Construction and Characterization
of Insect Cell-Derived Influenza VLP: Cell Binding, Fusion, and EGFP
Incorporation, Journal of Biomedicine and Biotechnology, 2010.

Vin NC & PT CNSH

25

Lp Cng ngh sinh hc K36

Trng HCT

Bo co mn Virus hc i cng

Robert A. Lamb and Robert M. Krug's (1996), Orthomyxoviridae: The Viruses and
Their Replication, in Fields Virology, Lippincott-Raven Publishers p1370.

Trang web

http://www.flu.gov ( 4/11/2012)
http://en.wikipedia.org/wiki/Influenza ( 4/11/2012)
http://virology-online.com/viruses/Influenza.htm, ( 4/11/2012)
http://fr.wikipedia.org/wiki/Grippe ( 4/11/2012)
http://www.impe-qn.org.vn/impe-

qn/vn/portal/InfoDetail.jsp?

area=58&cat=1101&ID=3194 ( 5/11/2012)
http://kahilas.blogspot.com/2011/08/swine-flu-faq.html ( 5/11/2012)
http://translate.google.com.vn/translate?
hl=vi&sl=fr&u=http://fr.wikipedia.org/wiki/Grippe&prev=/search%3Fq
%3Dgrippe%2Bvirus%26hl%3Dvi%26biw%3D1024%26bih%3D653%26prmd
%3Dimvns&sa=X&ei=JfyVUPUBaLniAepxoHQBg&sqi=2&ved=0CCEQ7gEwAA ( 5/11/2012)
http://translate.google.com.vn/translate?
hl=vi&sl=en&u=http://en.wikipedia.org/wiki/Virus&prev=/search%3Fq
%3Dstudies%2Bon%2Bthe%2Bvirus%2Bof%2Bscientists%26hl%3Dvi%26biw
%3D1024%26bih%3D653%26prmd
%3Dimvns&sa=X&ei=pMSYUM7CKMeWiQf6uYDYAg&ved=0CDsQ7gEwAg
( 5/11/2012)
http://www.microbiologytext.com/index.php?
module=Book&func=displayarticle&art_id=481 ( 9/11/2012)
http://xetnghiemdakhoa.com/diendan/printthread.php?tid=655 ( 11/11/2012)

Vin NC & PT CNSH

26

Lp Cng ngh sinh hc K36