Abstract
Toscana virus is an emerging bunyavirus in Mediterranean Europe where it accounts for 80% of pediatric meningitis cases during the summer. The negative-strand ribonucleic acid (RNA) genome of the virus is wrapped around the virally encoded nucleoprotein N to form the ribonucleoprotein complex (RNP). We determined crystal structures of hexameric N alone (apo) and in complex with a nonameric single-stranded RNA. RNA is sequestered in a sequence-independent fashion in a deep groove inside the hexamer. At the junction between two adjacent copies of Ns, RNA binding induced an inter-subunit rotation, which opened the RNA-binding tunnel and created a new assembly interface at the outside of the hexamer. Based on these findings, we suggest a structural model for how binding of RNA to N promotes the formation of helical RNPs, which are a characteristic hallmark of many negative-strand RNA viruses.
Highlights
Toscana virus is an enveloped negative-strand ribonucleic acid (RNA) virus that belongs to the genus phlebovirus in the Bunyaviridae family
We suggest a structural model for how binding of RNA to N promotes the formation of helical ribonucleoprotein complex (RNP), which are a characteristic hallmark of many negative-strand RNA viruses
Analytical gel filtration experiments combined with static light scattering indicated a tendency of the protein to self-assemble even in the absence of RNA (Figure 1A), unlike the N of the closely related Rift Valley Fever virus (RVFV), which exists as a dimer in solution [24]
Summary
Toscana virus is an enveloped negative-strand ribonucleic acid (RNA) virus that belongs to the genus phlebovirus in the Bunyaviridae family. Members of this genus include Rift Valley Fever virus (RVFV), Sandfly Fever Sicilian virus, Severe Fever with Thrombocytopenia Syndrome virus and Uukuniemi virus. These viruses are etiological agents of a wide range of illnesses ranging from selflimiting febrile episodes to hemorrhagic fevers characterized by multi-organ failure and death [1,2,3,4]. The S segment encodes a virulence determinant known as non-structural small protein NSs in the sense direction
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