en بیولوژی سلولی- مولکولی Cellular and Molecular Biology مروری Review article <div style="text-align: justify;"><strong>Background</strong>: The John Cunningham virus (JCV), a prevalent and asymptomatic virus, can cause neurological complications, such as progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals. Cancer is the second leading cause of death globally, with 10-15% of human cancers linked to viral infections, making JCV a significant tumor-inducing virus.<br> <strong>Objectives</strong>: This study aimed to examine the biology of JCV, its infection mechanisms, and the pathways that may facilitate tumorigenesis.<br> <strong>Methods</strong>: This narrative review employed a systematic approach to literature retrieval. Searches were conducted across major electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar, to identify relevant publications up to early 2025. The search scope included a wide range of study designs, such as original research, reviews, systematic reviews, meta-analyses, and case reports. The search strategy utilized a combination of the following key terms: &ldquo;John Cunningham virus&rdquo; OR &ldquo;JCV&rdquo;, &ldquo;JC virus&rdquo;, &ldquo;oncogenesis&rdquo; OR &ldquo;oncogenic&rdquo;, &ldquo;cancer development&rdquo;, &ldquo;infection&rdquo;, and &ldquo;human neoplasms.&rdquo;<br> <strong>Results</strong>: The findings indicate that JCV disrupts key cellular pathways, including p53 and retinoblastoma protein (pRB) pathways, and its genomic integration into host DNA suggests its oncogenic potential. Its mechanisms include alterations in cell cycle control and Wnt signaling, promotion of cell proliferation, and potential interaction with &beta;-catenin, leading to various cancers.<br> <strong>Conclusion</strong>: A better understanding of virus-related carcinogenesis could provide new targets for developing viral therapies that address not only viral infections but also cancer.</div> John Cunningham virus (JCV), Polyomavirus, Oncogenes, Retinoblastoma protein (pRB) 1 8 http://pbr.mazums.ac.ir/browse.php?a_code=A-10-1401-1&slc_lang=en&sid=1 Abolfazl Jafari-Sales a.jafari_1392@yahoo.com 100319475328460012015 100319475328460012015 Yes Department of Microbiology, Kaz.C., Islamic Azad University, Kazerun, Iran. Kosar Hosseini-Karkaj kosar22hosseini@gmail.com 100319475328460012016 0009-0001-1120-9665 No Infectious Diseases Research Center, TaMS.C., Islamic Azad University, Tabriz, Iran. Mehrdad Pashazadeh mehrdadpashazadeh85@gmail.com 100319475328460012017 0009-0005-0694-4592 No Infectious Diseases Research Center, TaMS.C., Islamic Azad University, Tabriz, Iran.