H u m a n

o nc o g e n i c
viru s e s
 Definition
• Viruses that produce tumors in there natural hosts or in
experimental animals, or induce malignant transformation
of cells in culture, are known as oncogenic viruses

• A DNA virus or RNA virus capable of causing malignant

transformation of cells, inducing a neoplasia in its host or
causally linked to human tumors
What is Cancer or Oncogenesis?

• An abnormal growth of tissue resulting from

uncontrolled, progressive multiplication of cells and
serving no physiological function; a neoplasm

• Is a disruption of the normal restrains on cellular

proliferation
• 20-30% of cancers are known to have viral etiology
Oncology : Study of Tumors
Oncogenesis : Process of development of tumor
Benign Tumors : Abnormal cell proliferation (localised) no
invasion
Malignant Tumor : Abnormal cell proliferation spreading
locally / metastatic (Lymphatic blood vessels)
Carcinoma : Malignant tumor of epithelial origin
Sarcoma : Malignant tumor of Mesenchymal origin
Lymphoma : Malignant tumor of Leucocytes origin
Cell transformation : Study of oncogenesis at molecular level
greatly facilitated by inducing essential
genetic changes in cultured cells

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 Human Cancer Viruses
• Contributing factor in at least 15% of human cancers
worldwide
• But as more research is done, this percentage is likely to be
found to be higher

 Associated with two tumours of great significance world-

wide:-

 Cervical carcinoma
 Hepatocellular carcinoma
 Cancer and cell transformation
• When the controlling regulatory mechanism
failed then the cell division continue without
differentiation and modification and mass of
cells are formed and this mass
ofcells(neoplasm) disturbs the sorrounding
cells.
• Cancer is a rapid, uncontrolled, abnormal
growth of cells
How the normal cell convert into cancerous
cell
• Inside the cell there is nucleus in which
chromosome is there where protooncogenes
is present in inactive state after mutation in
these genes protooncogenes is converted into
oncogenes.
 Interactions of
tumor viruses with
their hosts
• Oncogenic viruses cause mutation like changes in the host cell
by transformation
 Properties of cells transformed by viruses:

1. Alteration in shape
2. Increased growth rate
3. Loss of contact inhibition so that, instead of growing as
monolayer , they grow piled up, one over another, forming
“micro tumors”
4. Appearance of new virus specified antigens
5. Capacity to induce tumors in susceptible animals
Viruses can cause cancer
How??
Mechanisms of action by human
cancer viruses
 Two general patterns:
 Direct acting:- Virus introduces a new
transforming gene into the cell
 Indirect-acting:- Virus alters the expression of a
pre- existing cellular gene
 Oncogenic DNA Virus

• The viral DNA is integrated with the host cell genome as

prophage.
• As the integrated viral DNA is incomplete , no infectious virus
is produced, But under the influence, the host cell undergoes
neoplastic transformation .
 Oncogenic RNA Virus

• In case of oncogenic retroviruses, the viral RNA is converted

into double stranded DNA form by the action of an enzyme
reverse transcriptase ( RNA directed DNA polymerase )
• This double stranded DNA form of the retrovirus
genome is called provirus which become integrated
with cell genome.
• The integrated provirus may remain latent for variable
periods.
• Only when activated, it acts as template for viral RNA
synthesis and also induce cell transformation.
 Oncogenic viruses
DNA viruses

Papovavirus Herpes virus Hepatitis B Virus Poxvirus

•HPV •HSV 1&2 •Molluscum contagiosum
•Polyoma virus •CMV •Yaba virus
•Simian virus 40 •Epstein-Barr virus
 RNA viruses

Retrovirus Hepatitis C virus

•Avian sarcoma leukosis
•Murine leukosis virus
•Human T cell leukaemia virus
DNA Tumor Viruses In Human
Cancer
• Papilloma Viruses
• cause natural cancers in animals
• cause benign warts( noncancerous rough bumps that
form on the skin
• ubiquitous
• most human tumors are malignancies of epithelial
cells
• Papilloma viruses are found in 91% of women with
cervical cancer
• urogenital cancer
• Causes laryngeal, esophageal and anal carcinoma
Polyoma Viruses
• Polyoma - Mouse Leukemia,
• Human Polyomas (Jc And Bk) - Monkey Sarcoma
• Progressive Multifocal Leukoencephalopathy (Pml)
• Polyoma Virus Transforms Cells When The Genome Is
Incomplete

Simian virus 40
juvenile hamster sarcomas
Adenoviruses
• Highly oncogenic in animals

Herpes Viruses
Considerable evidence for role in human cancer
• Some very tumorigenic in animals
• Viral DNA found in small proportion of tumor cells

Epstein-Barr Virus
• Burkitt’s Lymphoma
• Nasopharyngeal cancer
• Infectious mononucleosis
• Transforms human B-lymphocytes in vitro
Hepatitis B Virus
• Vast public health problem
• 10% of population in underdeveloped countries are chronic
carriers
• Strong correlation between HBV and hepatocellular
carcinoma
• China: 500,000 - 1 million new cases of hepatocellular
carcinoma per year
RNA Tumor Viruses In Human
Cancer
Hepatitis C virus
Hepatocellular carcinoma

 Over half a million new cases annually

 Chronic Hepatitis B and C infection is the foremost cause

Human T-cell Lymphotropic viruses (HTLV)

 2 types: HTLV-1 and HTLV-2, share 60% of their genetic sequences

 HTLV-1: first retrovirus to be linked with the etiology of human

malignancy
 HTLV-3 and HTLV-4 recently discovered
 Virus family Virus Human cancer

Papillomaviridae Human papilloma viruses Genital tumours

Squamous cell carcinoma
Oropharyngeal carcinoma

Herpesviridae Epstein Barr Virus Nasopharyngeal carcinoma

Burkitt’s lymphoma
Hodgkin’s disease
B cell lymphoma

Human Herpesvirus 8 Kaposi’s sarcoma

Hepadnaviridae Hepatitis B virus Hepatocellular carcinoma

Retroviridae Human T cell lymphotropic virus Adult T cell leukemia

Human immunodeficiency virus AIDS-related malignancies
Flaviviridae Hepatitis C virus Hepatocellular carcinoma
 Oncogenes
Functionally - Those genes that are stimulatory
for growth and which cause cancer when
hyperactive.

• Oncogene: region of the viral genome that can

cause a tumor. The foreign gene causes changes
in the properties of the cell (eg.
Immortalization)
Viral Oncogene – V-onc
• Proto-oncogene: genes that are found in
all cells and its homologous is carried by
a virus
Cellular oncogene – C-onc

• V-onc is the viral counterpart of C-

onc
Role played by the virus
1. The virus carries the V-onc and transforms the
cell.
2. The virus does not carry v-onc but
hyperactivates C-onc already present in the
cell.

Both mechanisms - only by RETRO

VIRUSES

3. Transforming Oncogenic Retroviruses

4. Non Transforming Oncogenic Retroviruses
 Virus Oncogene

Rous sarcoma virus v-src

Simian sarcoma virus v-sis

Avian erythroblastosis virus v-erbA or v-erbB

Kirsten murine sarcoma virus v-kras

Moloney murine sarcoma virus v-mos

MC29 avian myelocytoma virus v-myc

 Anti-Oncogenes

Retinoblastoma gene has normal

regulatory function in many cells

Involved in
Retinoblastoma
Lung carcinomas
Breast carcinomas
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 Anti-Oncogenes

P53
Inactivated by
• deletion
• point mutation

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