The murine correlate of the Epstein-Barr and Kaposi's sarcoma-associated γ-herpesviruses, MHV-68, represents a valuable model to assess antiviral drug sensitivity and combinatorial drug synergies.

Authors

Christina Wangen, Debora Obergfäll, Katarína Briestenská, Jela Mistríková, William D Rawlinson, Manfred Marschall

Published in

Virus research. Pages 199799. Sep 12, 2026. Epub Sep 12, 2026.

Abstract

Human herpesviruses represent major human pathogens. Members of the γ-Herpesvirinae subfamily are of particular interest because they cause chronic diseases, such as cancers, by altering cellular processes and driving resting cells into a continuously proliferating phase. Also, autoimmune diseases such as multiple sclerosis have continuously been in the focus of interest. The prototypic human γ-herpesvirus, Epstein-Barr virus (EBV), has proven difficult to analyze for the development of antiviral therapies due to challenges associated with propagating the virus in vitro, phenotyping it, and assessment of antiviral phenotypic efficacy. Similarly, developing experimental systems to study the second human pathogenic virus in this subfamily, Kaposi sarcoma-associated herpesvirus (KSHV), has been challenging. The murine γ-herpesvirus 68 (MHV-68) is a well-characterized homolog of EBV and KSHV and represents a model virus for cell culture-based and animal-specific analyses. Here, we used MHV-68 to determine virus sensitivity to antivirals, and combinatorial drug synergies. Much of the recent information about novel antiherpesviral drugs has come from studies of human cytomegalovirus (HCMV). Therefore, a comparative analysis was also conducted between HCMV, MHV-68, and EBV. The study demonstrated: (i) successful establishment of a new MHV-68 replication model in murine and non-murine cell types; (ii) optimization of an MHV-68-specific quantitative readout based on the luciferase reporter system; (iii) assessment of mechanistically novel antiherpesviral compounds; (iv) comparative antiviral effects spanning the three respective herpesviruses; (v) analysis of antiviral drug combination treatments able to identify statistically significant drug synergies. Overall, the study provides new insights into molecular aspects of γ-herpesvirus replication, as well as antiviral drug development and targeting strategies.

PMID:
42731638
Bibliographic data and abstract were imported from PubMed on 13 Sep 2026.

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