Viral Viral CarcinogenesisCarcinogenesis

Solehah JeffreySolehah Jeffrey

06101080610108

Viruses Viruses infective Viruses infective Viruses

cancer cancer CancersCancers infectious??infectious??

OutlineOutline

1.1. OverviewOverview

2.2. HTLV-1 -Human T cell Leukemia HTLV-1 -Human T cell Leukemia Virus Type 1 Virus Type 1

3.3. HPV-Human PapillomavirusHPV-Human Papillomavirus

4.4. EBV- Epstein-Barr virusEBV- Epstein-Barr virus

5.5. KSHV/HHV-8 –Kaposi sarcoma KSHV/HHV-8 –Kaposi sarcoma Herpesvirus/ Human Herpes Virus-8 Herpesvirus/ Human Herpes Virus-8

6.6. HBV – Hepatitis B VirusHBV – Hepatitis B Virus

OverviewOverview

Additional factors Additional factors neededneeded

Peyton RousPeyton Rous

Viruses are responsible Viruses are responsible

for 12.83% of human cancers.for 12.83% of human cancers.

ONCOGENIC VIRUSESONCOGENIC VIRUSES

DNA oncogenic virusesDNA oncogenic viruses2.2. HPV- Cervical cancer (5.3%)HPV- Cervical cancer (5.3%)3.3. EBV- Burkitt’s Lymphoma, Hodgkin EBV- Burkitt’s Lymphoma, Hodgkin

Lymphoma, Nasopharyngeal ca., and B-Lymphoma, Nasopharyngeal ca., and B-cell Lymphoma (1.0%)cell Lymphoma (1.0%)

4.4. KSHV – Kaposi Sarcoma(1.5%)KSHV – Kaposi Sarcoma(1.5%)5.5. HBV – Liver cancer (5.0%)HBV – Liver cancer (5.0%)

RNA oncogenic virusesRNA oncogenic viruses1.1. HTLV-1 - Leukemia (0.03%) HTLV-1 - Leukemia (0.03%)

0.03 (Leukemia) 0.03 (Leukemia) +5.3 (Cervical cancer)+5.3 (Cervical cancer) +1.0 (Burkitt’s Lymphoma, Hodgkin +1.0 (Burkitt’s Lymphoma, Hodgkin

Lymphoma, Lymphoma, Nasopharyngeal ca., and Nasopharyngeal ca., and B-cell B-cell Lymphoma )Lymphoma )

+1.5 (Kaposi Sarcoma)+1.5 (Kaposi Sarcoma) +5.0 (Liver cancer)+5.0 (Liver cancer) =12.83% (total percentage of cancer =12.83% (total percentage of cancer

caused by caused by viral agent)viral agent)

HTLV-1 (Human T cell HTLV-1 (Human T cell Leukemia Virus Type 1)Leukemia Virus Type 1)

Transmission Transmission Blood productsBlood products Breastfeeding Breastfeeding Sexual contactSexual contact

Adult cell leukemia/ Adult cell leukemia/ lymphoma develops lymphoma develops in only 1% of in only 1% of infected individuals infected individuals

HTLV-I is endemic in HTLV-I is endemic in The CaribbeanThe Caribbean JapanJapan South AmericaSouth America parts of Africaparts of Africa

Strong tropism Strong tropism for T-cellsfor T-cells

HTLV-1 (Human T cell HTLV-1 (Human T cell Leukemia Virus Type 1)Leukemia Virus Type 1)

Region called Region called pXpX

TAX proteinTAX protein

IL-2IL-2

IL-2 receptorIL-2 receptor

GM-CSFGM-CSF

HPV (Human HPV (Human Papillomavirus)Papillomavirus)

Genital warts with low malignant potential : HPV 6 and 11Genital warts with low malignant potential : HPV 6 and 11

Over 60 genetically distinct typesOver 60 genetically distinct types

Benign warts : Type 1, 2,4, 7Benign warts : Type 1, 2,4, 7

HPV 16 : 64% of cervical HPV 16 : 64% of cervical cancercancer

HPV 18: 8% of cervical cancerHPV 18: 8% of cervical cancer HPV 16 + HPV 18 = 72% of HPV 16 + HPV 18 = 72% of

cervical cancer cervical cancer 55ThTh most frequent most frequent

cancer in womencancer in women

Risk factor:Risk factor: SmokingSmoking Immune Immune

suppressionsuppression X-ray radiationX-ray radiation

HPV (Human HPV (Human Papillomavirus)Papillomavirus)

HPVHPV E6E6

binds to Rb binds to Rb proteinprotein

inactivates inactivates p53 tumor p53 tumor suppressor suppressor genesgenes

Degrade BAXDegrade BAX

E7E7

induce cellular DNA synthesis induce cellular DNA synthesis Progression to S-phaseProgression to S-phase

release of E2F release of E2F transcription transcription factorfactor

EBV (Epstein-Barr virus)EBV (Epstein-Barr virus)

African form of African form of Burkitt lymphoma Burkitt lymphoma (Malaria)(Malaria)

B-cell lymphomas B-cell lymphomas (Immune deficiency)(Immune deficiency)

Nasopharyngeal Nasopharyngeal carcinoma (Salted carcinoma (Salted fish) fish)

Hodgkin lymphoma Hodgkin lymphoma (Unknown)(Unknown)

90% of adults infected90% of adults infected

Establish a lifelong latencyEstablish a lifelong latency

EBV (Epstein-Barr virus)EBV (Epstein-Barr virus) EBVEBV LMP-1LMP-1

prevents apoptosis prevents apoptosis by activating BCL-2by activating BCL-2

B-cell immortalizationB-cell immortalization

B-cell proliferationB-cell proliferation

KSHV(Kaposi sarcoma KSHV(Kaposi sarcoma Herpesvirus) Herpesvirus)

or HHV-8 (Human Herpes or HHV-8 (Human Herpes Virus-8)Virus-8)

Cancer of Cancer of lymphatic lymphatic endothelium endothelium

Kaposi Kaposi sarcoma sarcoma tumortumor Spindle cellsSpindle cells Highly Highly

vascular-vascular-abnormal abnormal dense and dense and irregular irregular blood vesselsblood vessels

Leak RBC Leak RBC into into surrounding surrounding tissuetissue

Kept under Kept under immunological control immunological control and only presents a and only presents a problem during problem during immunosuppression. immunosuppression.

Risk factors: Risk factors: HIV infectionHIV infection

KSHV(Kaposi KSHV(Kaposi sarcomaHerpesvirus) sarcomaHerpesvirus)

or HHV-8 (Human Herpes or HHV-8 (Human Herpes Virus-8)Virus-8)

HBV (Hepatitis B virus)HBV (Hepatitis B virus)

Risk factorsRisk factors smokingsmoking superinfection superinfection

with Hepatitis D with Hepatitis D virusvirus

aflatoxin Baflatoxin B

Far east, south east Far east, south east Asia, and AfricaAsia, and Africa

400 million 400 million infected worldwideinfected worldwide

HBV (Hepatitis B virus)HBV (Hepatitis B virus)

HBV HBV

Produce a viral Produce a viral protein called HBxprotein called HBx

Directs inactivation Directs inactivation of p53of p53

Inhibition of apoptosis

Cell immortalization

ConclusioConclusion…n…

Thank You Thank You !!!!

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life-results.htmllife-results.html