Atypical patterns of human cytomegalovirus infection and spread in U373 glioblastoma cells

• Published in: Virus research 2023-06, Vol.330, p.199112-199112, Article 199112
• Main Authors: Kalavacharla, Anusha, Koon, Chloe R., Freeman, MacKenzie R., Miller, William E.
• Format: Article
• Language: English
• Subjects: biopsy; Cytomegalovirus; Cytomegalovirus - genetics; Cytomegalovirus Infections; DNA; Genome, Viral; Glioblastoma; HCMV; Human betaherpesvirus 5; human population; Humans; Latency; Lytic replication; viability; viral genome; viruses
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2023.199112

•In cells derived from a GBM biopsy (U373), we found that HCMV does not spread throughout the culture and in fact, virus positive cells rapidly declined over time.•The viability of the infected GBM cells remained high over the time course.•Following HCMV infection of U373 GBM cells there is a rapid decline in the number of viral genomes over time.•In contrast to permissive cells such as fibroblasts, HCMV infection of U373 GBM cells leads to a self-limiting infection, whereby the virus fails to spread throughout the culture and the viral genome is subsequently lost. Human cytomegalovirus (HCMV) is ubiquitous in the human population, infecting >70% of people during the course of their lifetime. HCMV DNA and proteins have been detected in glioblastoma (GBM) tumor samples, but whether the virus is a driver of the malignant process or serendipitous passenger is not well understood. Traditionally, HCMV functions in a cytolytic fashion by proceeding through the lytic cycle and spreading viral particles to other cells. Our study focuses on understanding the pattern of HCMV infection and spread within GBM cells using an in vitro model. In cells derived from a GBM biopsy (U373), we found that HCMV does not spread throughout the culture and, in fact, virus-positive cells rapidly decline over time. Interestingly, the viability of the infected GBM cells remained high over the time course, and this was accompanied by a rapid decline in the number of viral genomes over the same time course. The implications of this atypical infection pattern and how this may affect GBM progression is discussed.