Oncovirus

the
cancerous agent

bhuvanesh611@gmail.com or
bhuvu4u@yahoo.co.in
Table of contents
1. Definition
2. History
3. Classification
4. Key words
5. Transformation
6. Oncogene
7. Replication
8. Example– DNA Oncovirus (HPV)
RNA Oncovirus (HTLV)
Defination:

*viral agents causing cancer in eukaryotic

animals by integrating in host genome
*A virus associated with malignancies in
natural host, experimental animals or cell
cultures.
*viruses which modified proto-oncogene,
obligatory host specific, with the ability
immortalization, possess genes which
stimulate growth and cause cancer.
Research History
In 1908, Ellerman &
Bang first
discovered virus,
producing leukemia
in chicken.
In 1911 Peyton Rous
1st shows the
presence of filterable
sarcoma material
that induce the
CANCER.
 Classification

Oncovirus

DNA oncogenic RNA oncogenic

viruses viruses
 DNA Oncov iruses
Virus Family Virus Associated tumours

Genital (Cervical, vulvar, penile)

warts, may progress to
Papovaviridae Papilloma * .carcinoma
Polyoma * Various carcinomas and sarcomas
SV40 ( Sarcoma(in Rodents

BK & JC * Polyoma in man, tumours in rodents

Herpesviridae ( Hepatitis simplex type (1 & 2 • Cervical carcinoma

Cytomegalovirus * Koposo's sarcoma, cervical neoplasia
,Nasopharyngeal carcinoma
Burkitt's lymphoma, B Cell
Epstein Barr virus * lymphoma

Hepatitis viruses Hepatitis B viruses * Primary hepatocelular carcinoma

Pox virus Molluscum contagiosum * Nodular epidermal hyperplasia

Shope fibroma * Fibroma
Yabavirus Nodular fibromatous hyperplasia
Adenoviridae Type 2, 5, 12 None in man, sarcomas in hemsters
 RN A
Oncovir use s

Retroviridae Avian sarcoma leucosis Various sarcomas, lymphomas and

virus (ALV) complex .lekaemia (natural tumours) in birds

Mouse leukaemia and

(sercoma (MLV . Various sarcomas, leukaemias

Various sarcomas, lymphomas in mice

(Feline leukaemis (Fel V and lekaemias

Bovine leukaemia Lymphosarcoma (B cells) in cattle

Human T Cell leukaemia *

((HTLA-1, 2 T-cell leukaemis/lymphoma in man

Flaviridae Hepatitis C virus * Primary hepatocellular carcinoma

 Oncogenic Viruses associated with human cancer

Virus family virus Type of malignancy

DNA VIRUS
Human papilloma Cervical, Valvular, Penile cancers
Papovaviridae virus of squamous cell type polyma

BK virus and JC virus Polyoma

Burkitt's lymphoma, cervical

Herpesviridae EB virus carcinoma

B-Cell lymphoma,
HSP type 2 Cevical carcinoma

RNA VIRUS

Flaviridae Hepatitis C virus Hepatocellular carcinoma

Retroviridae HTLV Adult T-Cell leukaemia

 Key Words
Immortalization : ability of virus to establish persistent
infection that can also stimulate uncontrolled cell growth
indefinitely provided that adequate nutrients are available.
Neoplasia: property of cell to undergo rapid, abnormal and
uncontrolled growth at the cost of remaining cells.
Permissive and Non-permissive cell
Malignancy
HeLa cell
Episomes
Transformation:
Ability of virus infected cell, to Change in the biological
functions of a cell by the regulation of viral genes to
cause malignant growth result in NEOPLASIA. these
change often (but not always) result from integration of
the viral genome into host cell genome.
Transformation of Normal cell to cancer
cell
 Characteristics of Transformed
cells:
► Possession of viral genome:
► Morphologic changes:
► Loss of cell-contact inhibition of growth:
► Increased efficiency of clone formation
► Decreased growth factor requirements:
► Change in membrane transport properties:
► Expression of tumour-associated antigen:
► Change in plasma membrane composition:
► Chromosomal alteration:
 Oncogene
► gene which encode for protein
► were first discovered in retroviruses
► proto-oncogenes exist naturally in the
human genome
► Functions:-
5. INDUCTION OF CELLULAR PROLIFERATION
6. INHIBITION OF CELLULAR PROLIFERATION
7. REGULATION OF PROGRAMMED CELL DEATH
 Type of Oncoviral infection
1. Productive : Synthesis and Release of
progeny virus.
a) Lytic—Host cell Killed e.g. DNA virus
b) Nonlytic—No noticeable cytopatic effect
on host cell e.g.. RNA virus

2. Non Productive : Progeny virus nor

produced
a) Abortive—loss of viral genome after
infection
b) Defective—viral genome incomplete
c) Non permissive—Host cell lack certain
factor
Multiplication of oncoviruses
► DNA Oncovirus:

► RNA Oncovirus:
In case of oncogenic DNA viruses:
► integrated with the host cell genome as
prophage
► encoded proteins which bind and
inactivate the growth-regulatory proteins
of the cell
► such as the retinoblastoma (RB) or p53
gene product
► cells bcl-2 oncogene prevents (apoptosis).
► defective or incomplete, no infections virus
is produced
 Multiplication of a RNA oncovirus
Reverse Capsid
transcriptase Envelope

Virus Two identical strands of RNA

1 Retrovirus penetrates
Host host cell.
cell
DNA of one of the host
cell’s chromosomes
5 Mature
retrovirus
leaves host Reverse
cell, acquiring transcriptase
an envelope as
it buds out.
Identical Viral RNA 2 Its RNA is
uncoated; reverse
strands of
transcription takes
RNA
place.
4 Transcription of the
provirus may also occur,
Viral proteins producing RNA for new
retrovirus genomes and
RNA that codes for the
RNA
retrovirus capsid and
envelope proteins.
3 The new viral DNA is
tranported into the host cell’s
nucleus and integrated as a
provirus. The provirus may
divide indefinitely with the
host cell DNA.
Provirus

Figure 13.19
► Examples
 CLASSIFICATION
► Phylum: Vira
► Sub Phylum: Deoxyvira
► Class: Deoxycubica
► Order: Haplovirales
► Group: Group I (dsDNA)
► Family: Papovaviridae
► Genus: Papillomavirus
► Strain : Human papillomavirus
► Papillomavirusesare a diverse group
of DNA-based viruses that infect the
skin and mucous membranes of
humans and a variety of animals

► Richard Shope
 TYPES
► More than 100 types of human
papilloma viruses (HPVs)
► HPVs 16, 18, 31, 33, 35, 39, 45, 50,
51,53, 55, 56, 58, 59, 64 and 68 are
considered “high risk” types
► HPV 16 and 18 are the most closely
associated with cervical carcinoma
► Some sexually transmitted HPVs -- types
6, 11, may cause genital warts
Structure
► small
► non-enveloped
► (~52-55nm
diameter )
► A single viral protein
(L1 ) necessary and
sufficient for
formation of a 60
nm capsid
composed of 72
star-shaped
GENOME
 GENE ORGANIZATION

► typically contains around 8000 bp

[7904 bp forHPV16 (GenBank®
accession number NC 001526)]
► organized in three regions:
• the early gene (E1 to E7)
• the late gene (L1 and L2)
• the upper regulatory region (URR)
► E1 : encode proteins that are vital for
extra chromosomal DNA replication and
the completion of the viral life cycle
► E2 : encodes two proteins - one, which
inhibits transcription of the early region;
and the other, which increases the
transcription of the early region
► E4 : Maturation, induces the collapse of
the cytoplasmic cytokeratin network in
human keratinocytes, stimulate
releasing
►
► E5 : interacts with various
transmembrane proteins like the
receptors of the epidermal growth
factor, platelet-derived growth factor,
and colony stimulating factor-1
► E6 and E7 :encode for oncoproteins
that allow replication of the virus and
the immortalization and
transformation of the cell that hosts
the HPV DNA.
► L1 and L2 : encode for viral capsid
proteins during the late stages of
virion assembly
 Regulation Mechanism
► E7 associates with pRb and disrupts
the association between pRb and the
E2F
► .E7 also associates with histone
deacetylases, components of the AP1
transcription complex and the cyclin-
dependent kinase inhibitors p21 and
p27.
► in the high-risk HPV types, both E6 and
E7 proteins are expressed together
from a single polycistronic mRNA
species.
► E7 block ARF (ADPribosylation factor)
pathway
► E6 PDZbinding can mediate
suprabasal cell proliferation and may
contribute to the development of
metastatic tumours by disrupting
normal cell adhesion
 Transmission
► By skin-to-skin or mucosa-to-mucosa
contact
► By sexual contact
► By mother to child during birth
Major steps in the development of
 HOW IT GIVES THE SYMPTOMS
OF CANCER

► “low risk” HPV gives warts on the

anus, vagina, vulva, penis and thighs.
► “intermediate risk” give lesion.
► “high risk” gives pre-cancerous lesions
and can lead to cancer of the cervix,
anus and other genital areas.
 DIAGNOSIS

1) Pap (Papanicolou) test : to detect

celular change.
*cells collected from the cervix (the
lower, narrow end of the uterus) to
detect cancer or abnormal cells that
may lead to cancer
2) Colloscopy :
3) DNA test :
 Prevention

• Absolutely no skin-to-skin sexual

contact
• The more sexual partners, the higher
the chance of contracting HPV.
• contraception
• Vaccination is now available to
prevent certain low risk types that
cause genital warts certain high risk
types that cause cancer.
 Treatment
► Cryotherapy – liq. N2
► Cautery – electrical current, laser
therapy
► Chemical treatments - drugs
► Surgery – removal
► Vaccination
 Production of prophylactic HPV virus-like
particle (VLP) vaccines

The vaccine mimics the virus shell

(Atomic force microscopy

image of a single VLP)

L1 capsomere
L1 L1 protein Virus-Like Particle (VLP)

5 x L1 72
capsomeres

Atomic force microscopy

5 x L1
image of a single VLP

Expression and self assembly

in a recombinant eukaryotic
L1-external protein
vector

Adapted from Syrjänen & Syrjänen. Papillomavirus infections in human pathology. Wiley
& Sons, Chichester; 2000. pp 11–46.
 HPV 16 VLP composed of 72
capsomere subunits of L1 protein
 Major Pharma developing
HPV VLP vaccines

Sanofi Pasteur MSD - Gardasil

 a quadrivalent HPV 6, 11, 16, 18 L1 VLP
vaccine; alum adjuvanted
 licensed in UK October 2006
 awaiting guidance from Joint Committee on
Vaccination and Immunisation (JCVI)
regarding policy for vaccination in the UK

GlaxoSmithKline - Cervarix
 a bivalent HPV 16, 18 L1 VLP vaccine; AS04
adjuvanted
 submitted to European Agency for the
Evaluation of Medicines (EMEA) March 2006
 BREIF DISCRIPTION OF RNA
VIRUS
► RNAoncovirus also calles as
oncornaviruses.
 Classification
► Phylum: Vira
► Sub Phylum: Ribovira
► Class: Ribocubica
► Order: Gymnovirales
► Group: RNA
► Family: Retroviridae
► Subfamily:
Orthoretrovirinae
► Genus: Deltaretrovirus
► Strain : Human T-cell leukemia virus
► Type : HTLV 1 & 2
► Infectionin T-cells
► Transmission
► Gives Adult T-cell leukemia (ATL)
► Composed of 2 copies of ssRNA
 References
► www.wikipedia.com
► www.iarc.uk
► www.cancerresearchuk.org
► www.cancer.gov
► https://cissecure.nci.nih.gov/
► www.nature.com
► Research paper by john Doorbar
► www.hpvinfo.com
► Online Microbiology and immunology books
► Research paper By Brandon Stott and Michelle
Wyse
► http://www.jem.org/cgi/
CONCLUSION
DISCUSSION
THANK YOU