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8/11/2019 Oncogenic Viruses CC
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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/8/11/2019 Oncogenic Viruses CC
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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
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Figure 3.1; 3.2 The Biology of Cancer( Garland Science 2007)
1909, Peyton Rou dico!er arco"a#inducing agent in
c$ic%en
2s cancer infectious32s cancer infectious3
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&o$anne Fi'iger
Paraite caued to"ac$ cancer
192 *o'el Pri+e icredited -or%
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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
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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
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1verview of viral replication1verview of viral replication
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6enome replication6enome replication
DNA viruses RNA viruses
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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
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v-myc and c-myc("yc oncogene)
How does tumourigenicity occur3How does tumourigenicity occur3
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u"an /a/illo"a !iru (P)u"an /a/illo"a !iru (P)
Dede (tree man)
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Human papilloma virus 8H
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carcinomacarcinoma
$&000&000 females
$00&000 females
'000 females
$00 females
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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
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2ntegration into the host genome2ntegration into the host genome
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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>)
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$ervical carcinoma progression$ervical carcinoma progression
; d = i i i
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; 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
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2nactivation of p@B "y =2nactivation of p@B "y =
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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@@(
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.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,
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$e 4ollo-ing lide are 4or
general interet onlyand
/ro!ide ot$er e>a"/le o4 * ?
R* !irue in oncogenei
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Flaviviridae
8hepatitis C virus
$C%5
Retroviridae
Human T-cell lymphotropic
virus (HTLV type I)
RNA virusesRNA viruses
@N( i
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@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
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Figure 3.17 The Biology of Cancer( Garland Science 2007)
@etroviral replication@etroviral replication
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Human 2mmunodeAciency 7irus H27
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H27 life cycle
See ani"ation at $tt/??---.roc$e#$i!.co"?$o"e?$o"e.c4"
H27 genome
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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
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8oure o4 in4ection
" ti t i l ti $/%
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"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
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Flaviviridae
8hepatitis C virus
$C%5
Retroviridae
Human T-cell lymphotropic
virus (HTLV type I)
RNA virusesRNA viruses
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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.jpg8/11/2019 Oncogenic Viruses CC
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hat causes hepatocellularat causes epatoce u arcarcinoma3carcinoma3
HB7 and H$7 co)infection3
HB7 integrates into genome and produces aproteinH"!, involved in H$$
H$7 does not integrate into the genome "utcan interact with host proteins and cause aninGammatory response, which cantransform cells
e.g. H$7 proteins N?and N>(can disrupttranscription factors leading to proliferationand inhi"ition of apoptosis
$C% lif l$C% lif l
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$C% life cycle$C% life cycle
H H Vi 8H H Vi 8 88$$%&'$$%&'
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Human Herpes Virus 8Human Herpes Virus 888$$%&' or$$%&' or
aposi!s sarcoma associated virus "HVaposi!s sarcoma associated virus "HV
Herpes virus family
Type ') causes9cold sores4 on lips
8I&E ofpopulation5
Type %) se!uallytransmitted diseasethat causes JcoldsoresJ on thegenitals 8 %>E ofU adults5.
H H Vi 8H H Vi 8 (($$%&' $$%&' * i4* i4
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Human Herpes Virus 8Human Herpes Virus 8(($$%&' a--a$$%&' a--a *aposi4s*aposi4s
sarcoma associated virussarcoma associated virus ende"ic region ende"ic region
* i4* i4
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*aposi4s sarcoma*aposi4s sarcoma
HH7F d t f tiHH7F d t f ti
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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 $u"an /rotein (e.g. !#cyc, !B)
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Herpesviridae
Human Herpes Virus
(HH7F5a.#.a *aposi4ssarcoma associatedvirus
pstein)Barr virus8B75
DNA virusesDNA viruses
E)% E i ) %iE)% E t i ) %i
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E)%( Epstein )arr %irusE)%( Epstein )arr %irus
most potent transforming agent,widespread in all human populations
usually carried as an asymptomatic persistentinfection (latent).
virus sometimes associated with thepathogenesis of certain types of lymphoid and
epithelial cancers, includingBurkitts lymphoma (BL),
Hodgkin disease and
Nasopharyngeal carcinoma(NPC).
Bur#itt4sBur#itt4s NasopharyngealNasopharyngeal Hodg#in4sHodg#in4s
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Bur#itt sBur#itt s
lymphomalymphomaNasopharyngealNasopharyngeal
carcinomacarcinomaHodg#in sHodg#in s
lymphomalymphoma
C0#60D o4 /atient
are
=E ero/oiti!e*P8 tiue tained 4or t$e
/reence o4 =E late
antigen.
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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
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in vivoin vivointeractions "etween B7 and hostinteractions "etween B7 and host
cellscells
f B7ummary of B7
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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