ViHiHippo · Viral hijacking of the Hippo pathway - HCMV-encoded viral GPCRs US28 and UL78 differentially modulate the Hippo pathway in cancer.

Viral hijacking of the Hippo pathway - HCMV-encoded viral GPCRs US28 and UL78 differentially modulate the Hippo pathway in cancer.

The ViHiHippo project aimed to address the critical issue of human cytomegalovirus (HCMV) and its potential role in cancer progression. HCMV is a herpesvirus with a high prevalence, infecting over 60% of the European population. While HCMV typically causes minimal symptoms in healthy individuals, recent studies have suggested that it may contribute to serious diseases such as heart disease and cancer. Notably, HCMV has been detected in tumor tissues but not in surrounding healthy tissues, and its presence is associated with increased tumor growth and poorer clinical outcomes in cancer patients. This underscores the urgent need to understand how HCMV influences cancer progression and to develop effective treatments targeting the latent HCMV pool. The primary objective of the ViHiHippo project was to elucidate the molecular mechanisms by which HCMV-encoded viral G protein-coupled receptors (vGPCRs), specifically US28 and UL78, modulate the Hippo signaling pathway. The Hippo pathway is crucial for regulating cell proliferation and organ growth, and its dysregulation is linked to cancer. Understanding how these vGPCRs hijack the Hippo pathway provided critical insights into HCMV's potential oncomodulatory effects. The project was structured to achieve the following specific objectives: 1. Identify and Characterize US28 Signaling: Investigate the signaling cascade that leads to US28-mediated regulation of the Hippo pathway, providing a foundational understanding of how US28 influences cell proliferation and tumor growth. 2. Investigate UL78 Signaling: Explore the signaling mechanisms of UL78, an atypical GPCR that does not activate classical G proteins, to uncover novel signaling routes through which UL78 modulates the Hippo pathway. 3. Characterize Combined Effects in Cancer: Examine the outcomes of US28 and UL78 modulation of the Hippo pathway in a viral cancer setting, including testing for potential complementary effects when both vGPCRs are co-expressed, to provide insights into their collective impact on cancer progression. The ViHiHippo project aligned with the European Union's strategic priorities in health research, particularly in understanding and combating cancer. By addressing the role of HCMV in cancer, this research contributed to the broader goals of reducing cancer incidence and improving patient outcomes. The project's significance was underscored by the high prevalence of HCMV and its potential impact on cancer progression. The results provided new therapeutic targets and strategies for managing HCMV-associated cancers, thereby supporting the EU's efforts to enhance public health and healthcare innovation.

Data: CORDIS, © European Union