Oncogenic Virus
Oncogenic virus
Virus that produce tumor in their natural
host, experimental animals or cell culture
Viruses associated with malignancies
DNA Virus:-
Papilloma virus, EBV, HBV
RNA virus:-
HTLV I,III, HCV
20% has viral risk factor
Terminologies
Immortalization – ability of the
virus to establish persistent infection, that can also stimulate uncontrolled
growth indefinitely
Transformation- ability of the virus infected
cell to cause malignant growth in immunodeficient or immunocompromised animals
Characteristic of transformed cells
Possession of viral genome
Integration or plasmid like
Morphological change
Loss of cell contact inhibition growth
Decrease growth factor requirement
Increase efficiency of clone formation
Changes in membrane transport properties
contd
Expression of tumor associated antigen
Changes in plasma cell membrane composition-
↓density & cellular glycolipids
↓fibronectin
↑oligosaccharides
Chromosomal alteration- partial deletion,
translocation & partial or complete duplication
Mechanism of viral oncogenesis
DNA virus :-
A portion is integrated in the host cell
genome
Encodes protein which binds & inactivate
growth regulatory protein (RB/p53 genes)
Loss of p53 gene product makes cell
susceptible to mutation
EBV – stimulates cell growth as B cell mitogen
and by inducing expression of bcl-2 oncogene, it prevents cell death
(apoptosis)
Mechanism of viral oncogenesis- contd
Integrated viral genome often has –
rearrangement or deletion
As viral DNA is defective or incomplete, no
infectious virus is produced
Host cell undergo neoplastic transformation
Retro viruses
Reverse transcriptase –
Construct DNA copy of RNA
DNA integrates with DNA of host
Adopts two approaches to oncogenesis
Encodes oncogenic proteins (sis, ras, src,
mos, myc, jun, fos)
These oncoproteins are identical to cellular
proteins
Stimulates cell growth ( Tumor)
Seen in animals ( not in human )
Second approach
HTLV
Encodes protein (tax)
Transactivates gene expression of T
lymphocytes
Clinical manifestation- DNA
DNA has
limited oncogenic potential
Viral genome codes for protein which
inactivates protein coded by tumor suppressor genes
Papova virus
HPV 6 & 11
benign warts and premalignant lesions
carcinoma of female and male genital tract
Herpes
Herpes simples 1 and 2 – cervical carcinoma
Virus causes insertional mutagenesis
EBV – Burkitt’s lymphoma, Nasopharyngeal
carcinoma
Transform lymphocytes to lymphoblast
Hepatitis B virus
Hepatocellular carcinoma
No oncogenes
Tumor cell contains integrated viral DNA
Probably acts by insertional mutagenesis or
transactivating
Oncogenic retro virus
Causes tumor of RE/haemopoietic system
Leukaemia/lymphoma
Oncogenes
Oncogene
is a gene that (when mutate or expressed at abnormally high level) contibutes
to the conversion of normal cell to cancer cell.
Oncogene
Viral oncogene (v-onc)- codes for protein that trigger transformation
of normal cells into malignant cells
Cellular oncogenes- oncogene isolated from
cancer cell
Proto-oncogene- counterpart in normal cell
Nomenclature
v- viral oncogene
c- cellular genes
v- src (sarcoma)
c- src
src- tyrosine specific protein
sis- platelet derived growth factor
mye- DNA binding protein
Function
Protein kinases- (v-src) codes for tyrosine
–specific kinase- loss of contact
inhibition
Transactivating proteins- over expression of
cellular replication and differentiation
Identification of oncogenes
Transfection-
NIH 3T3 mouse fibroblast
DNA probes
Antioncogenes
Tumor suppressor gene/growth suppressor gene/
anti-oncogenes
Retinoblastoma (Rb) gene
Retinoblastoma
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