Cellular Oxidative Stress Response Controls the Antiviral and Apoptotic Programs in Dengue Virus-Infected Dendritic Cells (PLoS Pathog. 2014 Dec 18;10(12):e1004566)

報告日期: 2015/03/31
報告時間: 16:00/16:50
報告學生: 賴彥仲
講評老師: 謝奇璋
附件下載: 下載[1460-1425857284-1.pdf] 

Cellular Oxidative Stress Response Controls the Antiviral and Apoptotic Programs in Dengue Virus-Infected Dendritic Cells

David Olagnier, Suraj Peri, Courtney Steel, Nadine van Montfoort, Cindy Chiang,Vladimir Beljanski, Michael Slifker, Zhong He, Carmen N. Nichols, Rongtuan Lin, Siddharth Balachandran, John Hiscott

PLoS Pathog. 2014 December; 10(12): e1004566.

Speaker: Yen-Chung Lai (賴彥仲)                       Time: 16:00 ~17:00, March 31, 2015

Commentator: Prof. Shieh, Chi-Chang(謝奇璋)   Place: 醫學院 602

Abstract:

Dengue virus (DENV) is the leading arthropod-transmitted viral infection in the world of tropics and subtropics, which causes 50 to 100 million infections, 500,000 cases of dengue haemorrhagic fever (DHF), and even 22,000 deaths annually.1 However, no effective vaccine or antiviral agent is available to prevent or treat against DENV infection. Reactive oxygen species (ROS) production is thought of as the marker of oxidative stress and the consequence of microbial invasion. Increased ROS generation has been described in virus infection which is linked with antiviral and inflammatory response2. Whereas, the redox of ROS homeostasis in dengue virus infection is not fully understood. In this study using a genome-wide transcriptome analysis, the authors found that IRF3/7/STAT1-driven antiviral response, NF-kB-triggered inflammatory network, as well as oxidative stress activation are the three major early responses identified in DENV2-infected human monocyte-derived dendritic cells (Mo-DC). During DENV infection, NADPH oxidase (NOX)-driven ROS generation not only potentiates antiviral response in early stage, but also triggers mitochondrial-dependent apoptosis in late infection period. The authors also found Nrf2, a transcription factor, plays a critical role in limiting DENV-induced antiviral and apoptotic responses by feedback modulation of oxidative stress. Silencing Nrf2 increased DENV-induced these responses. Taken together, the results demonstrated in this paper showed that the level of oxidative stress regulates both antiviral and apoptotic responses in DENV-infected Mo-DC, and provides a potential new target for treating DENV infection. 

References: 

  1. Gubler DJ. Dengue and dengue hemorrhagic fever. Clinical microbiology reviews 1998, 11(3): 480-496.
  2. Gonzalez-Dosal R, Horan KA, Rahbek SH, Ichijo H, Chen ZJ, Mieyal JJ, et al. HSV infection induces production of ROS, which potentiate signaling from pattern recognition receptors: role for S-glutathionylation of TRAF3 and 6. PLoS pathogens 2011, 7(9): e1002250.