Abstract
SummaryHantaviruses, a geographically diverse group of zoonotic pathogens, initiate cell infection through the concerted action of Gn and Gc viral surface glycoproteins. Here, we describe the high-resolution crystal structure of the antigenic ectodomain of Gn from Puumala hantavirus (PUUV), a causative agent of hemorrhagic fever with renal syndrome. Fitting of PUUV Gn into an electron cryomicroscopy reconstruction of intact Gn-Gc spike complexes from the closely related but non-pathogenic Tula hantavirus localized Gn tetramers to the membrane-distal surface of the virion. The accuracy of the fitting was corroborated by epitope mapping and genetic analysis of available PUUV sequences. Interestingly, Gn exhibits greater non-synonymous sequence diversity than the less accessible Gc, supporting a role of the host humoral immune response in exerting selective pressure on the virus surface. The fold of PUUV Gn is likely to be widely conserved across hantaviruses.
Highlights
Hantaviruses, from the family Bunyaviridae, constitute a genus of human pathogens with a near-worldwide distribution (Jonsson et al, 2010)
Expression of the Puumala hantavirus (PUUV) Gn ectodomain Similar to other hantaviruses (Schmaljohn et al, 1987), PUUV Gn encodes a signal sequence (Petersen et al, 2011), an N-terminal ectodomain, a predicted transmembrane region (Krogh et al, 2001), and a C-terminal cytoplasmic domain
Our PUUV Gn crystal structure was determined at pH 5.0, which is different than the pH used for the Tula virus (TULV) virion reconstruction
Summary
Hantaviruses, from the family Bunyaviridae, constitute a genus of human pathogens with a near-worldwide distribution (Jonsson et al, 2010). These viruses chronically and asymptomatically infect rodents, shrews, moles, and bats. Clinical symptoms of hantavirus infection usually manifest two to three weeks following initial exposure and lead to either hantavirus pulmonary syndrome (HPS) or hemorrhagic fever with renal syndrome (HFRS) (Lednicky, 2003). Hantaviruses have a lipid-bilayer envelope, and their negativesense RNA genome is divided into S, M, and L segments. Low resolution three-dimensional (3D) structures of Tula (TULV) and Hantaan virus spike complexes, derived by electron cryomicroscopy studies and combined with biochemical analysis, revealed that Gn and Gc form square-shaped oligomeric complexes on the virion envelope (Battisti et al, 2011; Hepojoki et al, 2010; Huiskonen et al, 2010)
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