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Oncgenic vireses :

Oncgenic vireses Vireses that produce tumors in their natural hosts or in experimental animals . induce malignant transformation of cells on culture

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Transformation – changes that accompany the conversion of a normal cell into malignant cell Altered cell morphology Fibroblast become short Parallel orientation is lost Chromosomal aberrations appear Altered cell metabolism Increased growth rate Increased production of organic acids + muco polysacharide Altered growth characteristics Loss of contact inhibitors Formation of heaped up growth (micro- tumour ) Cells divide indefinitely Antigenic alterations – neo antigens Animal inoculation – induce tumour

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HUMAN ONCOGENIC VIRUSES DNA viruses Papovavirus Papillomaviridae Polyomaviridae Simian vacuolating virus 40 BK and JC virus Poxviruses molluscum contagiosum virus yaba monkey tumor virus Adeno virus human adenoviruses Hepatitis B virus Herpes virus – Herpes simplex virus 1 (HSV-1) Herpes simplex virus 2 (HSV-2) Epstein-Barr virus (EBV) Cytomegalovirus (CMV) HHV-8 Kaposi's sarcoma-associated herpesvirus

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RNA viruses Hepatitis C virus (HCV) - flavi virus Human T- lymphotropic virus(HTLV ) Human papillomaviruses (HPV)-Cancers of cervix

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Oncogenic viruses malignanacy Human Papilloma Virus (HPV) condyloma acuminate HPV Cancers of cervix Polyoma virus Kidney cells BK and JC viruses Tumour in immuno deficiency pts

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Pox virus Molluscum contagiosum Yaba virus Histoplasma

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Herpes virus Epstein-Barr virus (EBV) Burkitt lymphoma Nasopharyngeal carcinomas Herpes simplex virus 1 (HSV-1) Carcinoma lip Herpes simplex virus 2 (HSV-2) Carcinoma cervix Cytomegalovirus (CMV) Carcinoma prostate HHV-8 Kaposi's sarcoma-associated herpesvirus Kaposi's sarcoma –

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Hepatitis B virus Hepatocellular carcinoma Hepatitis C virus Hepatocellular carcinoma

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Human T-cell leukemia virus (HTLV-1; HTLV-2) Adult T-cell leukemia Lymphoma

Papova virus :

Papova virus Pa – papilloma virus of human beings Po polyoma virus of mice Va – vaculating virus of monkey Small , non enveloped ,DNA viruses

Simian vaculating virus 40 (SV 40) :

Simian vaculating virus 40 (SV 40) Isolated from un inoculated rhesus and cyenomologus monkey kidney tissue cultures Produces prominent cytoplastic vaculation when inoculated into kidney cell cultures Oncogenic for newborn hamsters Medical importance – in preparation of live viral vaccines Live viral vaccines should be manufactured in monkey kidney tissue cultures tested and found free from SV 40 infection

Pailloma virus- species specific :

Pailloma virus- species specific Human papilloma virus infections only humans Grow only in organ cultures of human skin >70 types have been recognized based on genetic homology Serotypes 1,2,3,4 – verrucus vulgaris (common warts ) children adolescents hands of feet

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Serotypes 6, 11 – condylomata acuminata genital warts moists soft pedunculated HPV – malignancies in both sexes –seen on ext genitalia -- std and HIV pts Serotypes 6, 11 -intraepithelial neoplasia 16,18-> more severe invasive malignancies ca cervix and ca uterus

Human papova viruses :

Human papova viruses Poduce malignancies in patients with impaired immunity JC virus- isolated in 1971 from a patient hodgkins disease and progressive multifocal leuco encephalopathy(PML) Reported from USA UK FRANCE Grows only in human fetal glial cell cultures Oncogenic potential high Malignant gliomas I/C inoculation in newborn hamsters .

BK virus :

BK virus Isolated in 1971 from urine of a pt with kidney transplant Differs from JC virus Grows in a wide range of primary and continuous cell cultures Less oncogenic

BK and JC viruses :

BK and JC viruses Primary infection in child hood multiplication in brain and renal tract Reactivation from latent infection during immunodeficiency state

HTLV – human T cell leukemia virus :

HTLV – human T cell leukemia virus Belongs to retroviridae group Retro – reverse Presence of reverse trnscriptase enzyme During transcription –from RNA –RNA DNA hybrid-> DS DNA Lymphotropic viruses Infects T lymphocytes –CD4 + cells HTLV 1&2 –Adult T cell leukemia


HTLV Following blood transfusion and other methods of transfer of leukocytes Host specificity – infect only one species 3 types Ectotropic – multiply in native host species Amphotropic – native+ foreign Xenotrophic - only in foreign species

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Mode of transmission –exogenous – horizontal Endogenous - vertical

Oncogenes :

Oncogenes VIRAL ONCOGENES (V-ONC )/CANCER GENES CELLULAR ONCOGENES Viral oncogenes – genes which encode proteins triggering transformation of normal cell into malignant cell Cellular oncogenes isolated from cancer cells Proto oncogenes – similar genes found in normal cells -- not of viral origin -- seen in vertebrates and metazoa -- humans and fruit fly

Anti oncogenes / tumour suppressor genes :

Anti oncogenes / tumour suppressor genes A class of genes inn normal human cells function -> inhibition of malignant transformation Eg : Rb gene – loss of which is associated with retinoblastoma in children P 53 gene – tumour suppressor gene

Genomic structure of retrovirus:

Genomic structure of retrovirus Basic retroviral genome LTR LTR gag pol env

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Trans regulating retrovirus geome (HTLV) tat- trans activating gene LTR LTR gag pol env tat

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Acute transforming retrovirus Oncogene replacing part of basic genome- replication defective Cause – sarcoma ,carcinoma , leukemia Transform cells in culture LTR LTR onc

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Viral oncogenes Origin Natural tumour V- sarc Chicken Sarcoma V- ras Rat Sarcoma V- myc Chicken Leukemia V- fes Cat Sarcoma V-sis Monkey Sarcoma V- mos mouse Sarcoma

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Human oncogenes Chromosomal location V- sarc 20 V- ras 11 V- myc 8 V- fes 15 V-sis 22 V- mos 8

Mechanism of viral oncogenes :

Mechanism of viral oncogenes DNA viruses -> viral DNA/portion of viral DNA->integrated into host cell DNA-> under its influence host cell undergoes malignant transformation

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RNA viruses -> 2 mechanisms By indusing a new transforming gene ( oncogene )-> cellular genome By inducing or altering the expression of a pre existing cellular gene ->malignant transformation Other mechanisms Molecular mechanism Genetic mechanisms

Molecular mechanism:

Molecular mechanism Conversion of benign proto- oncogenes to cancer genes -> genes may get over expressed ->overproduced gene product giving rise to abnormal growth

Genetic mechanisms :

Genetic mechanisms Recombination between retroviral and cellular genes Promotor insertion Chromosomal trans location Gene amplification Mutation

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