The role of PTPIP51 protein in the regulation of cytomegalovirus infection
Project title: The role of PTPIP51 protein in the regulation of cytomegalovirus infection
Acronym: CMV-PTPIP51
Call title: Postdoctoral Research Projects
Call code: PDIP-2026
Funding source: Croatian Science Foundation
Applicant name: University of Rijeka, Faculty of Medicine, Ivana Bertović, PhD
Coordinator: Ivana Bertović, PhD
Project implementation period: 01.10.2026 – 30.09.2028
Total project value: EUR 100.000,00
Brief description:
Human cytomegalovirus (HCMV) causes severe congenital and life-threatening disease in immunocompromised individuals, yet no curative therapy or vaccine is available. A key gap in understanding CMV pathogenesis lies in how virus-induced remodelling of host cell architecture influences antiviral immunity. Cytomegaloviruses extensively reorganize intracellular membranes, including endoplasmic reticulum (ER)–mitochondria contact sites, which regulate calcium signalling, metabolism, and innate immune activation. However, the in vivo relevance of these structures during infection remains poorly defined.
This project focuses on PTPIP51, a mitochondrial outer membrane protein that regulates ER–mitochondria tethering. Using a novel PTPIP51-deficient mouse model, the study will determine whether disruption of ER–mitochondria contacts alters viral pathogenesis and host immune responses during murine cytomegalovirus (MCMV) infection, a well-established model of systemic CMV disease. Preliminary data indicate altered viral burden and cytokine responses in infected PTPIP51-deficient mice, supporting a functional role for ER–mitochondria regulation in antiviral immunity.
Systemic MCMV infection will be performed in wild-type and PTPIP51-deficient mice. Viral load will be quantified in target organs, together with serum cytokine profiling, flow cytometric immune phenotyping, and histological/confocal assessment of tissue pathology and viral dissemination. Bulk RNA sequencing will define host gene expression signatures associated with altered ER–mitochondria regulation during infection. Complementary mechanistic studies in primary bone marrow-derived macrophages will assess viral replication, signalling and cytokine production, including type I interferon responses, as well as macrophage activation. Key signalling pathways will be validated at the protein level.
This project will define how ER–mitochondria communication regulates systemic antiviral immunity and CMV infection outcomes. Expected outputs include a peer-reviewed open-access publication and high-value in vivo, transcriptomic, and mechanistic molecular insights, providing a foundation for future studies on organelle communication in infectious disease.
