Tumors and Cytomegalovirus: An Intimate Interplay

Human cytomegalovirus (HCMV) is a herpesvirus that alternates lytic and latent infection, infecting between 40 and 95% of the population worldwide, usually without symptoms. During its lytic cycle, HCMV can result in fever, asthenia, and, in some cases, can lead to severe symptoms such as hepatitis, pneumonitis, meningitis, retinitis, and severe cytomegalovirus disease, especially in immunocompromised individuals. Usually, the host immune response keeps the virus in a latent stage, although HCMV can reactivate in an inflammatory context, which could result in sequential lytic/latent viral cycles during the lifetime and thereby participate in the HCMV genomic diversity in humans and the high level of HCMV intrahost genomic variability. The oncomodulatory role of HCMV has been reported, where the virus will favor the development and spread of cancerous cells. Recently, an oncogenic role of HCMV has been highlighted in which the virus will directly transform primary cells and might therefore be defined as the eighth human oncovirus. In light of these new findings, it is critical to understand the role of the immune landscape, including the tumor microenvironment present in HCMV-harboring tumors. Finally, the oncomodulatory/oncogenic potential of HCMV could lead to the development of novel adapted therapeutic approaches against HCMV, especially since immunotherapy has revolutionized cancer therapeutic strategies and new therapeutic approaches are actively needed, particularly to fight tumors of poor prognosis.