Abstract
Human cytomegalovirus (HCMV) is a herpesvirus that infects between 40% and 95% of the population worldwide, usually without symptoms. 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 HCMV genomic diversity in humans. The high level of HCMV intra-host genomic variability could participate in the oncomodulatory role of HCMV 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; such HCMV strains are named high-risk (HR) HCMV strains. In light of these new findings, this review defines the criteria that characterize HR-HCMV strains and their molecular as well as the phenotypic impact on the infected cell and its tumor microenvironment.