Dengue structure differs at the temperatures of its human and mosquito hosts

Xinzheng Zhang, et al. PNAS. 110: 6795–6799, 2013.

Speaker: Yong-Shiang Cao (曹詠翔)                          Time: 15:00~16:00, Sep. 18, 2013

Commentator: Dr. Hsiao-Sheng Liu (劉校生 老師)  Place: Room 601

Abstract

Dengue virus (DENV) is one of the most significant human viral pathogens transmitted by mosquitoes. The diseases caused by DENV infection are range from fever, joint pain to more serious syndromes, such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). DENV exhibit different viral surface during its life cycle. The envelope E protein is the major component to form a trimer of prM-E heterodimers in immature virus, a dimer in mature virus, and a trimer in the fusogenic state. Mature DENV enters mammalian cells by receptor-mediated endocytosis. At membrane fusion, the E protein reassociates to a trimeric form by stimulation of low pH environment. Several neutralizing monoclonal antibodies (MAbs) bind to epitopes that are not exposed on the mature smooth virion at room temperature. The authors hypothesized that it is caused by viral surface conformational change during infection. To test this hypothesis and to understand conformational transition of DENV, the authors determined the DENV surface structures by using cryoelectron microscopy. They discovered that the increased temperature changes its viral surface from a smooth to a bumpy form when DENV enters to human hosts from mosquito. A corollary to this observation is that an optimal humoral response generated by DENV vaccine candidates for humans should induce antibodies that bind to and neutralize the bumpy form of the virus. This paper provides us important structural information that the bumpy virus should be used for   optimal design of dengue vaccine development.

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