Executive Summary : | The tripartite motif (TRIM) family proteins, comprising around 80 members, play a crucial role in antiviral response, autophagy, and cell survival. They also contribute to cell development and maturation during viral infection. Dengue virus (DENV) is the most common mosquito-borne flavivirus, causing dengue fever, severe hemorrhagic fever, and dengue shock syndrome. Some TRIM members have been investigated for their role in viral replication, such as TRIM5?, TRIM22, TRIM25, TRIM56, TRIM69, and TRIM79?. TRIM26 is critical for efficient Hepatitis C virus replication but not for DENV and Zika virus. Severe DENV infection results in a drop in platelet count, and megakaryocytes (MKs) produce platelets through a complex biological process called megakaryopoiesis. Autophagy is essential for normal megakaryopoiesis and participates in DENV replication. DENV downregulates GATA-1/2, NF-E2, survival signaling molecules, and innate receptors, which hamper platelet production. TRIM proteins may play a significant role in megakaryopoiesis, and their investigation could help develop novel therapies to modulate MK function toward platelet production. The project aims to determine the role of TRIM protein in megakaryopoiesis by identifying TRIM member/s that participate in megakaryopoiesis, examining their roles under cytokines/TPO and DENV infection, observing specific TRIM proteins' roles in innate immunity and interferon signaling after silencing upregulated TRIM during DENV infection, and using identified TRIM members for their interacting protein/s. This study may help define how these pathways can be manipulated in therapeutic settings to promote differentiation and modulate megakaryocyte function towards platelet production. |