Prothymosin α Accelerates Dengue Virus-induced Thrombocytopenia

Overview

Journal iScience

Publisher Cell Press

Date 2024 Jan 12

PMID 38213625

Authors

Mei-Lin Yang

Chia-Ling Lin

Yi-Cheng Chen

I-An Lu

Bing-Hua Su

Yen-Hsu Chen

Kuan-Ting Liu

Chao-Liang Wu

Ai-Li Shiau

Affiliations

Soon will be listed here.

Abstract

Thrombocytopenia is the hallmark finding in dengue virus (DENV) infection. Prothymosin α (ProT) has both intracellular and extracellular functions involved in cell cycle progression, cell differentiation, gene regulation, oxidative stress response, and immunomodulation. In this study, we found that ProT levels were elevated in dengue patient sera as well as DENV-infected megakaryoblasts and their culture supernatants. ProT transgenic mice had reduced platelet counts with prolonged bleeding times. Upon treatment with DENV plus anti-CD41 antibody, they exhibited severe skin hemorrhage. Furthermore, overexpression of ProT suppressed megakaryocyte differentiation. Infection with DENV inhibited miR-126 expression, upregulated DNA (cytosine-5)-methyltransferase 1 (DNMT1), downregulated GATA-1, and increased ProT expression. Upregulation of ProT led to Nrf2 activation and reduced reactive oxygen species production, thereby suppressing megakaryopoiesis. We report the pathophysiological role of ProT in DENV infection and propose an involvement of the miR-126-DNMT1-GATA-1-ProT-Nrf2 signaling axis in DENV-induced thrombocytopenia.

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