Suppressive effect of dengue virus envelope protein domain III on megakaryopoiesis

Virulence

Te-Sheng Lien¹  Mei-Tzu Su¹  Chi-Yuan Liao²  Po-Kong Chen³  Guan-Ling Lin³  Hao Chan³  Hsin-Hou Chang⁴  Der-Shan Sun⁴ 

[1] Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien, Taiwa;Department of Obstetrics and Gynecology, Mennonite Christian Hospital, Hualien, Taiwa;Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwa;Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwa;Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien, Taiwa;

关键词: apoptosis;    autophagy;    dengue virus;    envelop protein domain III;    megakaryocytic differentiation;    megakaryopoiesis;    thrombocytopenia;   

DOI  :  10.1080/21505594.2017.1343769

来源: Taylor & Francis

【 摘 要 】

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.

【 授权许可】

Unknown