Immunoevasion strategies of cytomegalovirus: Modulation of MHC I and cytotoxic lymphocytes

Ongoing Projects, Projects

 

Project title: Immunoevasion strategies of cytomegalovirus: Modulation of MHC I and cytotoxic lymphocytes

Call title: Installation Research Projects

Call code: UIP-2025-02-2353

Funding source: Croatian Science Foundation

Applicant name: University of Rijeka, Faculty of Medicine

Coordinator: Asst. Prof. Jelena Železnjak, PhD

Research Team, University of Rijeka Faculty of Medicine:

  • Asst. Prof. Paola Kučan Brlić, PhD
  • Tina Ružić, PhD
  • Magdalena Medved

Project implementation period: 01.04.2026 – 31.03.2031

Total project value: EUR 299.420,00

Brief description:

Cytomegalovirus (CMV) is a widespread ß-herpesvirus that can persist in its host for a lifetime. One of its main strategies to evade immune response involves modulation of major histocompatibility complex class I (MHC I) molecules, thereby affecting cytotoxic T lymphocytes (CTLs) and innate immune cells (NK cells) responses. Among the viral proteins involved in this process, MATp1, encoded by the most highly expressed transcript of murine CMV (MCMV), partners with m04 protein, to modulate MHC I expression, ensuring effective inhibition of NK cells via inhibitory Ly49 receptors. However, our preliminary data indicate that CMV utilizes MATp1 not only to regulate NK cell responses, but also to modulate antigen presentation, potentially reducing the quality of the presented peptides on MHC I molecules. Accordingly, in vivo infection model with the wild-type MCMV exhibits a weaker CD8 T-cell response compared to a MCMV lacking MATp1, suggesting its role in immune evasion.The aim of this study is to elucidate the mechanisms of MATp1 modulation of MHC molecules and to investigate how peptide quality affects the adaptive immune response. Since CMV is being explored as a platform for vaccine development, unraveling its immune evasion tactics could advance antiviral strategies. This is particularly important for HCMV-based adoptive T-cell therapy (ACT), which utilizes virus-specific CTLs to control infection in immunocompromised patients. Improved understanding of how CMV manipulates MHC I and antigen presentation may lead to more precise therapeutic protocols and optimized CD8 T-cell response.