Abstract
Bleeding is a clinical characteristic of severe dengue and may be due to increased vascular permeability. However, the pathogenesis of severe dengue remains unclear. In this study, we showed that the Rac1-microfilament signal pathway was involved in the process of DENV serotype 2 (DENV2) infection in EAhy926 cells. DENV2 infection induced dynamic changes in actin organization, and treatment with Cytochalasin D or Jasplakinolide disrupted microfilament dynamics, reduced DENV2 entry, and inhibited DENV2 assembly and maturation. Rac1 activities decreased during the early phase and gradually increased by the late phase of infection. Expression of the dominant-negative form of Rac1 promoted DENV2 entry but inhibited viral assembly, maturation and release. Our findings demonstrated that Rac1 plays an important role in the DENV2 life cycle by regulating actin reorganization in EAhy926 cells. This finding provides further insight into the pathogenesis of severe dengue.
Highlights
Dengue virus (DENV) belongs to the family Flaviviridae and is one of the most widespread mosquito-borne human pathogens worldwide, especially in tropical and subtropical countries
Compared with mock-treated cells, pretreatment with Cytochalasin D (Cyto D) and Jas induced approximately 22% and 30% decreases in viral entry (Figure 1A), respectively, and these decreases were significant (P
These decreases from the level of mock-treated cells were significant (P
Summary
Dengue virus (DENV) belongs to the family Flaviviridae and is one of the most widespread mosquito-borne human pathogens worldwide, especially in tropical and subtropical countries. The course of this illness may become complicated and result in the life-threatening clinical form of the disease, i.e., severe dengue This condition includes dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), which are characterized by systemic hemorrhage and increased capillary permeability. A morphological study identified hemorrhage, edema and swollen vascular endothelial cells (VECs) in several organs in fatal dengue patients, and viral antigens and negative-strand RNA were detected in VECs, hepatocytes and macrophages (Povoa et al, 2014). This finding indicated that increased vascular permeability and morphological changes of VECs are characteristic pathological features of severe dengue
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have