HCV

1. HPV Oncogenesis
 On persistence of infection with high risk HPV types, the viral DNA is integrated
into the target epithelial cells.
 This results in genomic instability of the host cell leading to loss of E2 viral
repressor and overexpression of viral oncoproteins E6 and E7.
 These oncoproteins(E6 and E7) from high risk HPVs have high affinity for target
hosts cell than these oncoproteins from low risk HPVs.
 Transforming effects of HPV are largely due to alteration in genes encoding E6 and
E7 oncoproteins as followings

2. HPV-E6 Degrades TP53 Blocks apoptosis TERT overexpressed
(Tumor- suppressor
inhibited)
HPV-E7 Binding to RB Inactivates p21, p27 Activates cyclin D, C,CDK4
(RB- E2F
Displaced)
(CDK Inhibiters)
Oncogenic Effects of E6
Oncogenic Effects of E7
• Immortalization
• Excessive proliferation
• Genomic instability
• Immortalization
• Excessive proliferation
• Genomic instability

3. EPSTEIN-BARR VIRUS(EBV)
 EBS infects human B-lymphocytes and epithelial cells and long-term infection
stimulates them to proliferate and develop into malignancies of corresponding
cells. EBV is implicated in the following human tumours:
i. Burkitt lymphoma,
ii. Anaplastic nasopharyngeal carcinoma,
iii. Post-transplant lymphoproliferative disease,
iv. Primary CNS lymphoma in AIDS patients, and
v. Hodgkin lymphoma

4. Burkitt Lymphoma
 Burkitt lymphoma was initially noticed in African children by Burkitt in 1958 but is
now known to occur in 2 forms.
 African endemic form
 Sporadic form (seen else where in world)
 It usually occurs in children in between the age of 3-14 years. It responds favorably
to chemotherapy.
 The association between Burkitt lymphoma and EBV is observed from the following
features.
 Over 90% of Burkitt lymphomas are EBV-positive in which the tumour cells carry the viral
DNA.
 100% cases of Burkitt lymphoma show elevated levels of antibody titres to various EBV
antigens.
 EBV has strong tropism for B lymphocytes. EBV-infected B cells grown in cultures are
immortalizes, i.e. they continue to develop further along B-cell-line to propagate their
progeny in the altered form.

5. EBV-induced oncogenesis
B lymphocyte
(EBV-infected)
Cell proliferation
dysegulated
(CD40-like effect)
LMP1 expressed Activates BCL2
Growth signalling
Prevents apoptosis
Epithelial cell
(EBV-infected)
Elaborates EBNA-2
(via NF-kB, JAK/stat pathway)
Activates cyclin
D,SRC family
Stimulates B-cell
proliferation
Burkitt Lymphoma
Nasopharyngeal
carcinoma

7. Anaplastic nasopharyngeal carcinoma
 This is the other tumour having involvement of EBV infection.
 The tumour is prevalent in South-East Asia, especially in the Chinese, and in
Eskimos.
 The evidence linking EBV infection with this tumour is as follows:
i. 100% cases of nasopharyngeal carcinoma carry DNA of EBV in nuclei of tumour cells.
ii. Individuals with this tumour have titres of antibodies to various EBV antigens.

8. HUMAN HERPESVIRUS 8 (HHV-8)
 It has been shown that infection with HHV-8 is associated with Kaposi sarcoma, a
vascular neoplasm common in patients of AIDS.
 Hence also called Kaposi sarcoma-associated herpesvirus(KSHV).
 Compared to sporadic Kaposi sarcoma, the AIDS-associated tumour is multicentric
and more aggressive.
 HHV-8 has lymphotropism and is also implicated in etiology of pleural effusion
lymphorma and multicentric variant of Castleman disease.

9. HHV-8 (KSHV) ONCOGENESIS
 This is explained as under:
i. Viral DNA is seen in nuclei of all tumour cells in Kaposi sarcoma.
ii. There is overexpression of several KSHV oncoproteins by latently infected cells: v-
cyclin, v-interferon regulatory factor(v-IRF) and LANA(latency-associated nuclear
antigen).
iii. These viral proteins cause increased proliferation and survival of host cells and
thus induce malignancy.