Cryo-EM structure of the mature dengue virus at 3.5-Å resolution

Zhang, X. et al. Nat. Struct. Biol. 20, 105-111 (2013).

Speaker: Chin-Kun Tsai (蔡進焜)                                 Time: 13:00~14:00, Mar.13, 2013

Commentator: Dr. Shang-Rung Wu (吳尚蓉 老師)    Place: Room 601

Abstract

Dengue virus (DENV) is a mosquito-borne flavivirus that causes many life-threatening disease including hemorrhagic fever and shock syndrome. It causes about 50 million infections per year worldwide¹.Currently, no effective therapies or vaccines are available to against DENV infection. DENV membrane proteins, envelope (E) and pre-membrane (prM) play critical roles during virus maturation and infection². The spiky immature form of of a DENV particle consists of 60 E trimers, and it undergoes conformational changes to produce the ’smooth mature’ DENV virion that is composed of 90 E dimers during maturation in different pH environments³. However, changes in pH results in the dramatic changes in structural and transitional transformations of DENV membrane proteins during maturation and infection are not clear. The authors provided the cryo-elecronmicroscopy (EM) structure of the whole DENV virion at 3.5 Å resolution to explain the interaction of E and M. They found the N-terminal 20-amino-acid loop of M (M_1-20) latches E to prevent premature exposure of its fusion peptide by pH-sensing histidine residues during viral maturation at acidic pH in trans-Golgi network (TGN). But M releases the latch site and trigger E expose fusion peptide to initiate viral infection in the late endosome. Taken together, M chaperones E to undergo dramatic conformational changes when viral maturation and infection, and this interaction is pH-dependent process.

References

1.      WHO. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control (WHO, Geneva, Switzerland, 2009).

2.      Yu, I.M. et al. Structure of the immature dengue virus at low pH primes proteolytic maturation. Science 319, 1834–1837 (2008).

3.      Li, L. et al. The flavivirus precursor membrane-envelope protein complex: structure and maturation. Science 319, 1830–1834 (2008).