A Possible Role of Human Herpes Viruses Belonging to the Subfamily Alphaherpesvirinae in the Development of Some Cancers

Seroepidemiological studies suggest that human herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) are linked with several types of cancer; however, they do not appear to play a direct role and are considered to be cofactors. The abilities of HSV-1 and -2 to transform cells in vitro can be demonstrated by suppressing their lytic ability via irradiation with a specific dose of ultraviolet light, photoinactivation in the presence of photosensitizers (e.g., neutral red or methylene blue), and culture under specific conditions. Several mechanisms have been proposed to explain the actions of these viruses. According to the hit-and-run mechanism, viral DNA initiates transformation by interacting with cellular DNA and thereby inducing mutations and epigenetic changes, but is not involved in other stages of neoplastic progression. By contrast, according to the hijacking mechanism, viral products in infected cells can activate signaling pathways and thereby cause uncontrolled proliferation. Such products include RR1PK, an oncoprotein that activates the Ras pathway and is encoded by the HSV-2 gene ICP10. Virus-encoded microRNAs may act as cofactors in tumorigenesis of serous ovarian carcinoma and some prostate tumors. Herpes virus-associated growth factors that facilitate or suppress transformation may play important roles in tumor formation. Finally, there is much evidence that HSV-2 increases the risk of cervical cancer after infection of human papilloma viruses. Key words: HSV-1 - HSV-2 - cancer - mechanisms of transformation This work was supported by APVV 0621-12. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 29. 11. 2016 Accepted: 20. 3. 2018.