Suppressive Effect of Dengue Virus Envelope Protein Domain III on Megakaryopoiesis

Overview

Journal Virulence

Specialty Microbiology

Date 2017 Jun 17

PMID 28622093

Citations 16

Authors

Guan-Ling Lin

Hsin-Hou Chang

Te-Sheng Lien

Po-Kong Chen

Hao Chan

Mei-Tzu Su

Chi-Yuan Liao

Der-Shan Sun

Affiliations

Soon will be listed here.

Abstract

Dengue virus (DENV) infection can cause severe, life-threatening events, and no specific treatments of DENV infection are currently approved. Although thrombocytopenia is frequently observed in dengue patients, its pathogenesis is still not fully understood. Previous studies have suggested that DENV-induced thrombocytopenia occurs through viral-replication-mediated megakaryopoiesis inhibition in the bone marrow; however, the exact mechanism for megakaryopoiesis suppression remains elusive. In this study, a reductionist approach was applied, in which C57B/6J mice were inoculated with recombinant DENV-envelope protein domain III (DENV-EIII) instead of the full viral particle. Our results demonstrated that DENV-EIII-suppressed megakaryopoiesis is similar to those observed with DENV infection. Furthermore, in agreement with our in vivo analyses, DENV-EIII sufficiently suppressed the megakaryopoiesis of progenitor cells from murine bone marrow and human cord blood in vitro. Additional analyses suggested that autophagy impairment and apoptosis are involved in DENV-EIII-mediated suppression of megakaryopoiesis. These data suggest that, even without viral replication, the binding of DENV-EIII to the cell surface is sufficient to suppress megakaryopoiesis.

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