Table 1 Direct oncogenic mechanisms exploited by human herpesviruses
From: Implication of human herpesviruses in oncogenesis through immune evasion and supression
Human herpesvirus | Associated cancers | Direct oncogenic mechanisms |
|---|---|---|
Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) | HSV1 was detected in benign and malignant thyroid tumours [3], associated with prostate cancer, melanoma incidence in both men and women [4], associated with cervical cancer [5] | Induces unscheduled DNA synthesis [6]. In lytically infected cells, both HSV-1 and HSV-2 possess an anti-apoptotic activity, specifically HSV-2 protein ICP10PK, which inhibits apoptosis through activation of Ras/Raf-1/MEK/ERK pathway [7] |
Human herpesvirus 3, or Varicella zoster virus | Leukaemia, lymphoma, skin cancer, benign and malignant breast tumours [8] | VZV ORF12 activates AP1, a transcription factor that upregulates cellular proliferation [9]. VZV ORF63 inhibits apoptosis by IE63 protein [10] |
Human herpesvirus 4, or Epstein-barr virus (EBV) | Nasopharyngeal Carcinoma, Burkitt’s Lymphoma and Hodgkin’s lymphoma, to lesser extent | RASSF1A promoter methylation, p16 homozygous deletions andmethylation [11, 12] |
HIV-positive CNS lymphomas and hypopharyngeal and laryngeal tumours [13–15], rarely post-transplant smooth muscle tumours [16] | ||
Human herpesvirus 5, or human cytomegalovirus | Glioblastoma (90% association), lymphoma, nasopharyngeal cancer, cervical cancer, Kaposi’s sarcoma (KS), colorectal carcinoma, prostate cancer, skin cancer, astrocytomas [17, 18] | Inducing cell cycle progression, activation cell motility and migration, induces VEGF expression, inhibiting DNA damage repair, inducing chromosomal aberrations, inhibiting apoptotic pathways [2] |
Human herpesviruses 6 and 7 (HHV6 and HHV7), or roseoloviruses | Paediatric lymphoma [19]), acute lymphoblastic leukaemia [20], basal cell carcinoma [21], glioma [22] | Restrains p53 [23], DR7 transform NIH3T3 cells [24], cell cycle arrest at G2/M phase [25], integrate into human chromosome [22] |
Human herpesvirus 8, or Kaposi’s sarcoma associated virus (KSHV) | Kaposi’s sarcoma, Multicentric castleman disease (MCD), Primary effusion lymphoma (PEL) | vIRF3 and ORF73 (LANA) inhibit p53-mediated cell cycle arrest and apoptosis; K13 (ORF71) inhibits extrinsic death-receptor-mediated apoptosis pathway; ORF16 encodes the viral Bcl-2 protein that inhibits apoptosis and suppresses the cellular autophagy pathway [26] |