oncogenic viruses cc

8/11/2019 Oncogenic Viruses CC

1/44

Oncogenic viruses

These slides provide an overview of the role ofoncogenic viruses in cancer progression

Dr. Momna Hejmadi, University of Bath

N.B. ome images used in these slides are from thete!t"oo#s listed and are not covered under the

$reative $ommons license as et

This resource created "y Dr. Momna Hejmadi, University of Bath, %&'&, islicensed under the $reative $ommons (ttri"ution)Non)$ommercial)hare (li#e%.& U*+ ngland - ales /icense.

To view a copy of this license, visithttp+00creativecommons.org0licenses0"y)nc)sa0%.&0u#0
http://creativecommons.org/licenses/by-nc-sa/2.0/uk/http://creativecommons.org/licenses/by-nc-sa/2.0/uk/


2/44

1ncogenic viruses1ncogenic viruses

Key Concepts

Normal cells infected with certain

viruses can "e transformed intocancer cells due to e!pression oractivation of viral oncogenes

Transformation can result inintegration of viral genes or genomesinto the host genome


3/44

Figure 3.1; 3.2 The Biology of Cancer( Garland Science 2007)

1909, Peyton Rou dico!er arco"a#inducing agent in

c$ic%en

2s cancer infectious32s cancer infectious3


4/44

&o$anne Fi'iger

Paraite caued to"ac$ cancer

192 *o'el Pri+e icredited -or%


5/44

Figure 3.7a The Biology of Cancer( Garland Science 2007)

Normal cells infected with certain virusesNormal cells infected with certain viruses

can "e transformedcan "e transformed


6/44

Tumour virus implicated asTumour virus implicated as

aetiological agents for every 1 inaetiological agents for every 1 in

6 human cancers!!6 human cancers!!Family Example Tumour type

""

er/e!iridae Human Herpes V8#$$%&'

Epstein()arr virus#E)%'

*aposi4ssarcoma

Hodg#in4s

lymphoma

""

Pa/o!a!iridae human papillomavirus #$*%'

$ervicalcarcinoma

""

e/adna!iridae hepatitis ) virus(#$)%'

/ivercarcinoma

R* Flaviviridae $epatitis C virus$C%5

R* Retroviridae Human T-cell #cell leu%ae"ia


7/44

1verview of viral replication1verview of viral replication


8/44

6enome replication6enome replication

DNA viruses RNA viruses


9/44

How does tumourigenicity occur3How does tumourigenicity occur37iral genomes show the presence of several human

gene homologues 8cellular proto)oncogenes5

2nfective viruses 9#idnap4 proto)oncogenes which arethen transformed into oncogenes

e.g. c)src0v)src : v)myc0c)myc : v2/;0 2/; 8interleu#in ;5


10/44

v-myc and c-myc("yc oncogene)

How does tumourigenicity occur3How does tumourigenicity occur3


11/44

u"an /a/illo"a !iru (P)u"an /a/illo"a !iru (P)

Dede (tree man)


12/44

Human papilloma virus 8H


13/44

carcinomacarcinoma

$&000&000 females

$00&000 females

'000 females

$00 females


14/44

HPV life c!cleHPV life c!cle

n4ection eta'li$ed in 'aal e/it$elial layer -$ere !iral

geno"e "aintained a an e/io"e

iral re/lication occur in u/ra'aal layer

n4ection are t$ere4ore long lating


15/44

2ntegration into the host genome2ntegration into the host genome


16/44

HPV $ "roduces onl! eit "roteinsHPV $ "roduces onl! eit "roteins

1$ Re"lication of viral DNA2 maintenance of virale"isome2 essential for viral re"lication andcontrol of ene transcri"tion

13 1ssential for viral re"lication2re"ression of 1 and 1,

1 4orms filamentous c!to"lasmic net/or5s

1 Prevents acidification of endosomes2interaction /it 1"idermal 6ro/t 4actor

(164) 7Platelet#Derived 6ro/t 4actor(PD64)

8R :riin of DNA re"lication2 reulation of HPVene e;"ression

Protein 4unction

8$ inds to DNA

1 Destruction of " tumor su""ressor "rotein

1, ?nactivation of Retino>lastoma tumor su""ressor "rotein (R>)


17/44

$ervical carcinoma progression$ervical carcinoma progression

; d = i i i


18/44

; and = proteins inactivate tumour suppressor; and = proteins inactivate tumour suppressor

proteins p>? and p@Bproteins p>? and p@B

ran4or"ing acti!ity o4 P1 lin%ed to 1 and 1, /rotein

1 and 1,inter4ere -it$ tu"our u//reor acti!ity


19/44

2nactivation of p@B "y =2nactivation of p@B "y =
http://mmbr.asm.org/content/vol68/issue2/images/large/zmr0020420560003.jpeg


20/44

Pre!entati!e 4or cer!ical cancer in c$ildrenaged 9516 year and -o"en 4ro" 1#2

year

nearly 100 /ercent e44ecti!e in /re!enting

/recancerou cer!ical leion,

/recancerou !aginal and !ul!ar leion

and genital -art caued 'y in4ection -it$t$e P ty/e , 11, 1 or 1 in -o"en

'et-een t$e age o4 1 and 2.

6ardasil6ardasil@@(


21/44

.eading

8$a/ter Biolo! of ancer >! RA Weinberg(dditional reading

:ncogenic !irue 'y Dennis J McCance

---.el.net o- -ill P !accine a44ect cer!ical cancer

Roden R,


22/44

$e 4ollo-ing lide are 4or

general interet onlyand

/ro!ide ot$er e>a"/le o4 * ?

R* !irue in oncogenei


23/44

Flaviviridae

8hepatitis C virus

$C%5

Retroviridae

Human T-cell lymphotropic

virus (HTLV type I)

RNA virusesRNA viruses

@N( i


24/44

@N( viruses@N( viruses Unsta"le @N(

genome

prone tomutations

6eneratesgenetic diversity

and escapeantiviral therapy $an "e

oncogenic8e.g.hepatitis $virus H$75

@ i l li i


25/44

Figure 3.17 The Biology of Cancer( Garland Science 2007)

@etroviral replication@etroviral replication


26/44

Human 2mmunodeAciency 7irus H27


27/44

H27 life cycle

See ani"ation at $tt/??---.roc$e#$i!.co"?$o"e?$o"e.c4"

H27 genome


28/44

H27 genome3 structural genesgag8group speciAcantigen5 encodes matri!,capsid, nucleocapsidproteinspol8polymerase5 encodesreverse transcriptase,integrase, protease

env8envelope5 encodessurface - transmem"raneproteins6 regulatory genesrev8regulatory virusprotein5tat8transactivator5nef8negative regulatoryfactor5vif, vpr, vpu, env8envelope5 encodes surface

- transmem"rane protein


29/44

8oure o4 in4ection

" ti t i l ti $/%


30/44

"ntiretroviral or anti $/%therapy

(ll approved anti)H27 drugs attempt to "loc# viral replication

within cells "y inhi"iting either @T or H27 protease.

Nucleoside analogues mimic H27 nucleosides preventing DN(

strand completion e.g. idovudine 8(T5, dd2, dd$, tavudine

Non nucleoside @T inhi"itors 8NN@T25 e.g Delavirdine and

Nevirapine


31/44

Flaviviridae

8hepatitis C virus

$C%5

Retroviridae

Human T-cell lymphotropic

virus (HTLV type I)

RNA virusesRNA viruses


32/44

hepatitis $ virushepatitis $ virus $C%$C%

(ects ?E of glo"al population

2nfects primarily hepatocytes>&)F&E of infected individuals go on to develop hepatocellular

carcinoma 8H$$5

(t least ; genotypes #nown

hat causes hepatocellularat causes epatoce u ar
http://www.nih.go.jp/niid/virology2/HCV001.jpg


33/44

hat causes hepatocellularat causes epatoce u arcarcinoma3carcinoma3

HB7 and H$7 co)infection3

HB7 integrates into genome and produces aproteinH"!, involved in H$$

H$7 does not integrate into the genome "utcan interact with host proteins and cause aninGammatory response, which cantransform cells

e.g. H$7 proteins N?and N>(can disrupttranscription factors leading to proliferationand inhi"ition of apoptosis

$C% lif l$C% lif l


34/44

$C% life cycle$C% life cycle

H H Vi 8H H Vi 8 88$$%&'$$%&'


35/44

Human Herpes Virus 8Human Herpes Virus 888$$%&' or$$%&' or

aposi!s sarcoma associated virus "HVaposi!s sarcoma associated virus "HV

Herpes virus family

Type ') causes9cold sores4 on lips

8I&E ofpopulation5

Type %) se!uallytransmitted diseasethat causes JcoldsoresJ on thegenitals 8 %>E ofU adults5.

H H Vi 8H H Vi 8 (($$%&' $$%&' * i4* i4


36/44

Human Herpes Virus 8Human Herpes Virus 8(($$%&' a--a$$%&' a--a *aposi4s*aposi4s

sarcoma associated virussarcoma associated virus ende"ic region ende"ic region

* i4* i4


37/44

*aposi4s sarcoma*aposi4s sarcoma

HH7F d t f tiHH7F d t f ti


38/44

HH7F and transformationHH7F and transformation @ot /eo/le in4ected -it$ do not get AS

""unou//reed indi!idual are uce/ti'le iral $o"ologue o4 e!eral $u"an /rotein (e.g. !#cyc, !B)


39/44

Herpesviridae

Human Herpes Virus

(HH7F5a.#.a *aposi4ssarcoma associatedvirus

pstein)Barr virus8B75

DNA virusesDNA viruses

E)% E i ) %iE)% E t i ) %i


40/44

E)%( Epstein )arr %irusE)%( Epstein )arr %irus

most potent transforming agent,widespread in all human populations

usually carried as an asymptomatic persistentinfection (latent).

virus sometimes associated with thepathogenesis of certain types of lymphoid and

epithelial cancers, includingBurkitts lymphoma (BL),

Hodgkin disease and

Nasopharyngeal carcinoma(NPC).

Bur#itt4sBur#itt4s NasopharyngealNasopharyngeal Hodg#in4sHodg#in4s


41/44

Bur#itt sBur#itt s

lymphomalymphomaNasopharyngealNasopharyngeal

carcinomacarcinomaHodg#in sHodg#in s

lymphomalymphoma

C0#60D o4 /atient

are

=E ero/oiti!e*P8 tiue tained 4or t$e

/reence o4 =E late

antigen.


42/44

B7 genome and host cell transformationB7 genome and host cell transformation

=E#encoded nuclear antigen 2 (=E*2)

latent "e"'rane /rotein 1 (B@P1)"i"ic 8C0 rece/tor

B@P2 "i"ic t$e E cell rece/tor

in vivoin vivo interactions "etween B7 and hostinteractions "etween B7 and host


43/44

in vivoin vivointeractions "etween B7 and hostinteractions "etween B7 and host

cellscells

f B7ummary of B7


44/44

aetiolo! of several different l!m"oid ande"itelial malinancies.

1BV#encoded latent enes induce B#cell

transformationin vitro >! alterin cellular enetranscri"tion and constitutivel! activatin 5e!

cell#sinallin "at/a!s.

1BV e;"loits te "!siolo! of normal B#cell

differentiation to "ersist /itin te memor!#B#

cell "oolof te immunocom"etent ost.

ummary of B7ummary of B7

oncogenic viruses cc

Documents