Structure of west nile virus

S Mukhopadhyay, BS Kim, PR Chipman… - Science, 2003 - science.org
S Mukhopadhyay, BS Kim, PR Chipman, MG Rossmann, RJ Kuhn
Science, 2003science.org
West Nile virus (WNV) is found throughout Africa, Europe, Central Asia, and, most recently,
in North America. The first outbreak in the United States was in New York City during the
summer of 1999, and the virus subsequently spread across the United States (1). In 2002,
there were 4156 reported cases of human illness associated with WNV and 284 deaths.
WNV is a flavivirus transmitted primarily by Culex mosquitoes to vertebrate hosts.
Flaviviruses include members such as dengue virus, yellow fever virus, and tick-borne …
West Nile virus (WNV) is found throughout Africa, Europe, Central Asia, and, most recently, in North America. The first outbreak in the United States was in New York City during the summer of 1999, and the virus subsequently spread across the United States (1). In 2002, there were 4156 reported cases of human illness associated with WNV and 284 deaths. WNV is a flavivirus transmitted primarily by Culex mosquitoes to vertebrate hosts. Flaviviruses include members such as dengue virus, yellow fever virus, and tick-borne encephalitis virus and are positivestrand RNA viruses that contain three structural proteins and a host-derived lipid bilayer. Two lineages of WNV (I and II) have been identified (2). All isolates that cause severe human disease fall into lineage I. With the use of cryoelectron microscopy (cryo-EM) and image reconstruction techniques, we have determined a 17 Å resolution structure of WNV New York 99, the strain responsible for the outbreak in the United States (3). The virus has icosahedral symmetry and is 500 Å in diameter with no surface projections or spikes (Fig. 1A), which are prominent on other envelope-containing viruses such as influenza, HIV, and measles virus. A cross-sectional view (Fig. 1B) shows concentric layers of density indicating the multilayer organization of the virus. The outermost layer contains the highest density and corresponds to the E and M transmembrane proteins. The 35 to 40 Å thick lipid bilayer appears nonspherical with the transmembrane components of the M and E proteins visible. The nucleocapsid core contains multiple copies of the capsid protein and the genome RNA.
The major surface protein E is responsible for receptor binding, host membrane fusion, and can elicit a neutralizing antibody response. Although the atomic structure of the WNV E protein is not known, structures of the ectodomains of the closely related dengue and tick-borne encephalitis virus E proteins
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