Dengue virus envelope glycoprotein structure: New insight into its interactions during viral entry

Amajor step in understanding the molecular interactions that lead to entry of enveloped viruses into their target cells is obtaining structural information on the viral surface glycoproteins at the atomic level. In addition to carrying the main antigenic determinants of the virus, these proteins are responsible for the major steps involved in the entry process, which involve receptor recognition and fusion between viral and cellular membranes. A huge step forward in the field was made >20 years ago, when the laboratories of Don Wiley and John Skehel obtained the crystal structure of the influenza virus hemagglutinin (HA) (1), which carries both receptor-binding and membrane fusion functions. Since then, the x-ray structures of relatively few soluble ectodomains of viral glycoproteins have been determined, compared to the exponential increase of protein structures deposited in the Protein Data Bank in the same period. In particular, structural information on viral envelope proteins combining both receptor-binding and membrane fusion functions is very scarce. Over the years, only the structures of the tick-borne encephalitis (TBE) flavivirus major envelope (E) protein (2) and of the influenza C virus HA-esterase glycoprotein (3) were added to the database. In this issue of PNAS, Modis et al. (4) report the crystal structure of the E protein from dengue virus, a mosquito-borne flavivirus responsible for the highest rate of disease and mortality among members of this viral genus. This structure is therefore a very important addition to the current repertoire. Dengue virus is the most important arthropod-borne human pathogen. The incidence of dengue fever epidemics has increased dramatically over the last few decades (5), and it is estimated that up to 100 million cases occur annually. In addition, a severe form of the disease, dengue hemorrhagic fever (DHF), has emerged in the same period causing ≈ 500,000 cases worldwide each year …

[1]  I. Wilson,et al.  Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolution , 1981, Nature.

[2]  T. Monath,et al.  Dengue: the risk to developed and developing countries. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[3]  S. Harrison,et al.  Structural basis for membrane fusion by enveloped viruses. , 1999, Molecular membrane biology.

[4]  S. Harrison,et al.  The envelope glycoprotein from tick-borne encephalitis virus at 2 Å resolution , 1995, Nature.

[5]  Mike Carson,et al.  Ribbon models of macromolecules , 1987 .

[6]  C. King,et al.  Analysis of the steps involved in Dengue virus entry into host cells. , 1999, Virology.

[7]  G. Wengler,et al.  The membrane proteins of flaviviruses form ion-permeable pores in the target membrane after fusion: identification of the pores and analysis of their possible role in virus infection. , 2003, The Journal of general virology.

[8]  J. Navaza,et al.  The Fusion Glycoprotein Shell of Semliki Forest Virus An Icosahedral Assembly Primed for Fusogenic Activation at Endosomal pH , 2001, Cell.

[9]  R. Steinman,et al.  DC-SIGN (CD209) Mediates Dengue Virus Infection of Human Dendritic Cells , 2003, The Journal of experimental medicine.

[10]  Lam Sk,et al.  Dengue and dengue hemorrhagic fever. , 1990 .

[11]  Y. Modis,et al.  A ligand-binding pocket in the dengue virus envelope glycoprotein , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[12]  J. L. Nieva,et al.  Fusion of Semliki Forest virus with cholesterol-containing liposomes at low pH: a specific requirement for sphingolipids. , 1995, Molecular membrane biology.

[13]  Wei Zhang,et al.  Structure of Dengue Virus Implications for Flavivirus Organization, Maturation, and Fusion , 2002, Cell.

[14]  J. Skehel,et al.  Structure of the haemagglutinin-esterase-fusion glycoprotein of influenza C virus , 1998, Nature.