Princeton: Host-Microbe Dynamics

Treatment options for human cytomegalovirus (HCMV) remain limited, and host telomerase has been implicated in the pathogenesis and oncogenesis of multiple herpesviruses, including HCMV, motivating Princeton’s Notterman Lab to investigate the effect of telomerase inhibition on HCMV replication and the mechanism of the interaction between HCMV and host telomerase.  They found that HCMV infection increases host telomerase activity, at least in part, through modulation of human telomerase reverse transcriptase expression during earlier phases of the HCMV replication cycle.  Telomerase inhibition strongly reduced viral titer for two HCMV strains in a dose-specific manner.  Telomerase inhibition reduces viral gene and protein expression across the HCMV replication cycle, as well as suppressed viral genome replication and viral infectivity.  The results strongly indicate a biologically meaningful role for telomerase in supporting HCMV active infection, specifically by supporting viral replication and infectivity, and suggest the potential for a novel clinical anti-viral treatment for active HCMV infection. 

Cavanaugh CM, Betsinger CN, Katchur N, Zhang S, Yang K, Nogalski M, Cristea IM, Notterman D. Effect of host telomerase inhibition on human cytomegalovirus. J Virol. 2025 Mar 18;99(3):e0157824. doi: 10.1128/jvi.01578-24. Epub 2025 Feb 5. PMID: 39907284; PMCID: PMC11915825.  https://journals.asm.org/doi/full/10.1128/jvi.01578-24?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org