TUMOR VIRUSES

1. VIRUSES CAN CAUSE BENIGN OR MALIGNANT

TUMORS IN MANY SPECIES OF ANIMALS AND
MAMMALS. DESPITE THE COMMON
OCCURRENCE OF TUMOR VIRUSSES IN
ANIMALS ONLY A FEW VIRUSSES ARE
ASSOSIATED WITH HUMAN TUMORS AND
EVIDENCE THAT THEY ARE TRULLY THE
CAUSATIVE AGENTS EXISTS FOR VERY FEW
2. TUMOR VIRUSES HAVE NO CHARACTERISTIC
SIZE, SHAPE, OR CHEMICAL COMPOSITION
3. SOME ARE LARGE, SMALL, ENVELOPED, AND
OTHERS ARE NAKED (NON ENVELOPED), HAVE
DNA AND OTHERS RNA
4. THE FACTORS ARE UNITES ALL OF THEM IS THEIR
COMMON ABILITY TO CAUSE TUMORS
 MALIGNANT TRANSFORMATION OF
CELLS
• MALIGNANT TRANSFORMATION REFERS TO
CHANGES IN THE GROETH PROPERTIES, SHAPE,
AND OTHER FEATURES OF THE TUMOR CELLS
• MALIGNANT TRANSFORMATION CAN BE
INDUCED BY TUMOR VIRUSES NOT ONLY IN
ANIMALS BUT ALSO IN CULTURED CELLS. IN
CULTURE, THE FOLLOEING CHANGES OCCURE
WHEN CELLS BECOME MALIGNANTY
TRANSFORMED
 ALTERED MORPHOLOGY
• MALIGNANT CELLS LOSS THEIR CHARACTERISTIC
DIFFERENTIATED SHAPE AND APPEAR ROUNDED
AND MORE REFRACTILE WHEN SEEN IN A
MICROSSOPE
• THE ROUNDING IS DUE TO THE DISAGGREATION
OF ACTIN FILAMENTS, AND THE REDUCED
ADHERENCE OF THE CELL TO THE SURFACE OF THE
CULTURE DISH IN THE RESULTS OF CHANGES IN
THE SURFACE CHARGE OF THE CELL
 FEATURES OF MALIGNANT
TRANSFORMATION
FEATURED DESCRIPTION
• LOSS OF DIFFERENTIATED SHAPE
ALTERED MORPHOLOGY ROUNDED AS A RESULT OF
DISSAGGRTEATATION OF ACTIN
FILAMENTS AND DECREASED
ADHESION TO SURFACE
• MORE REFRACTILE

• LOSS OF CONTACT INHIBITION OF

ALTERED GROWTH GROWTH
• LOSS OF CONTACT INHIBITION OF
MORPHOLOGY MOVEMENT
• REDUCED REWUIREMENT FOR SERUM
GROWTH FACTORS
• INCREASED ABILITY TO GROW IN
SUSPENSION
• INCRESEAD ABILITY TO CONTINUE
 • INDUCTION OF DNA SHYNTESIS
ALTERED CELLULAR • CHROMOSOMAL CHAMGES
PROPERTIES • APPEAREANCE OF NEW ANTIGEN
•INCREASED AGGLUTINATION BY
LECTINS

• REDUCED LEVEL OF CYCLIC AMP

ALTERED BIOCHEMICAL • ENHANCED SECRETION OF
PROPERTIES PLASMINOGEN ACTIVATOR
• INCREASED ANAEROBIC GLYCOLISIS
• LOSS OF FIBROMECTIN
• CHANGES IN GLYCOPROTEIN AND
GLYCOLIPIDS
 ROLE OF TUMOR VIRUSES IN
MALIGNANT TRANSFORMATION
• MALIGNANT TRANSFORMATION IS A PERMANENT
CHANGE IN THE BEHAVIOR OF THE CELL. MUST THE
VIRAL GENETIC MATERIAL BE PRESENT AND
FUNCTIONING AT ALL TIMES OR CAN IT ALTERS SOME
CELL COMPONENT AND NOT BE REQUIRED
SUBSEQUENTLY
• THE ANSWER TO THIS QUESTION WAS OBTAINED BY
USING A TEMPERATURE- SENSITIVE MUTANT OF
ROUSSAR COMA VIRUS.THIS MUTANT HAS AN
ALTERED TRANSFORMING GENE THAT IS
FUNCTIONAL AT THE LOW PERMISSIVE
TEMPERATURE (35°C) BUT NOT AT THE HIGH,
RESTRICTIVE TEMPERATURE (39°C)
•ALTHOUGH MALIGNANT
TRANSFORMATION IS A PERMANENT
CHANGE REVERTANTS TO NORMALITY DO
APPEAR, ALBEIT RARELY. IN THE
REVERTANS STUDIED, THE VIRAL GENETIC
MATERIAL REMAIN INTEGRATED IN
CELLULAR DNA, BUT CHANGES IN THE
QUALITY AND QUANTITY OF THE VIRUS-
SPECIFIC RNA OCCURE
 PROVIRUS AND ONCOGENESIS
• THE TWO MAJOR CONCEPTS OF THE WAY VIRAL TUMOR
GENESIS OCCURS ARE EXPRESSED IN THE :
-PROVIRUS
- ONCOGENE
THIS CONTRASTING IDEAS ADDRESS THE FUNDAMENTAL
QUESTION OF THE SOURCE OF THE GENES FOR
MALIGNANCY
1.IN THE PROVIRUS MODEL, THE GENES ENTER THEY CELL
AT THE THINGS OF INFECTION BY THE TUMOR VIRUS
2.IN THE ONCOGENE MODEL THE GENES FOR MALIGNANCY
ARE ALREADY PRESENT IN ALL CELLS OF THE BODY BY
VIRTUE OF BEING PRESENT IN THE INITIAL SPERM AND EGG
BOTH PROVIRUSES AND ONCOGENE MAY PLAY
A ROLE IN MALIGNANT TRANSFORMATION.
EVIDENCE FOR THE PROVIRUS MODE CONSISTS
OF TINDING COPIES OF VIRAL DNA INTEGRATED
INTO CELL DNA ONLY IN CELL THAT HAVE BEEN
INFECTED CELLS HAVES NO CORES OF THE VIRAL
DNA
 WELCOME OF TUMOR VIRUS INFECTION
• IS DEPENDENT ON THE VIRUS AND TYPE OF CELL
• SOME TUMOR VIRUSSES GO THROUGH THEIR
ENTIRE REPLICATIVE CYCLE WITH THE
PRODUCTION OF PROGRNY, VIRUS, WHERE AS
OTHERS UNDERGROUND INRTERRUPTED CYCLE,
ANA LOGOUS TO LYSOGENY IN WHICH OF THE
PROVIRAL DNA IS INTEGRATED INTO CELLULAR
DNA AND LIMITED EXPRESSION APPROVIRAL
GENES OCCUR
•THERE FOR MALIGNANT TRANSFORMATION IS
EXPRESSION OF THE “EARLY” GENES OF THE
VIRUS
 CHARACTERISTIC DNA VIRUS RNA VIRUS

PROTOTYPE VIRUS SV 40 ROUS SARCOMA VIRUS

NAME OF GENE EARLY-REGION A GENE src GENE

NAME OF PROTEIN T ANTIGEN Src GENE

FUNCTION OF PROTEIN KINASE, PROTEIN KINASE THAT

PROTEIN ATPASE PHOSPORYLATES
ACTIVITY,BINDING TO TYROSINE
DNA, AND
STIMULATION OF DNA
SYNTHESIS

LOCATION OF PRIMARILY PLASMA MEMBRANE

PROTEIN NUCLEAR,BUT SOME
IN PLASMA
MEMBRANE
REQUIRED FOR VIRAL YES NO
REPLICATION
CHARACTERISTIC DNA VIRUS RNA VIRUS
GENE HAS NO YES
CELLULAR
HOMOLOG
 EVIDENCE FOR HUMAN TUMOR
VIRUSES
• HUMAN T-CELL LHYMPOTROPIC VIRUS
HTLV1 AND HTLV 2 → ASSOCIATED WITH LEUKIMIA
AND LHYMPHODAS
• HUMAN PAPILLOMA VIRUSES (HPV)
→ PAPILLOMA WARTS
• EPSTEIN – BARR VIRUSSES
→ BURKITTS LHYMPHOMA
• HEPATITIS B VIRUSSES
→ HEPATOMA
• HEPATITIS HERPES VIRUS B
→KAPOSIS SARCOMA-ASSOCIATED HERPES VIRUS
ANIMAL TUMOR VIRUSES

1. DNA TUMOR VIRUSES

- PAVPOVAVIRUSES
- ADENOVIRUSES
- HERPESVIRUSES

2. RNA TUMOR VIRUSES (RETROVIRUSES)