Abstract
Rift Valley fever phlebovirus (RVFV; Phenuiviridae, Phlebovirus) is an important mosquito-borne pathogen of both humans and ruminants. The RVFV genome is composed of tripartite, single stranded, negative or ambisense RNAs. The small (S) segment encodes both the nucleocapsid protein (N) and the non-structural protein (NSs). The N protein is responsible for the formation of the viral ribonucleoprotein (RNP) complexes, which are essential in the virus life cycle and for the transcription and replication of the viral genome. There is currently limited knowledge surrounding the roles of the RVFV nucleocapsid protein in viral infection other than its key functions: N protein multimerisation, encapsidation of the RNA genome and interactions with the RNA-dependent RNA polymerase, L. By bioinformatic comparison of the N sequences of fourteen phleboviruses, mutational analysis, minigenome assays and packaging assays, we have further characterised the RVFV N protein. Amino acids P11 and F149 in RVFV N play an essential role in the function of RNPs and are neither associated with N protein multimerisation nor known nucleocapsid protein functions and may have additional roles in the virus life cycle. Amino acid Y30 exhibited increased minigenome activity despite reduced RNA binding capacity. Additionally, we have determined that the N-terminal arm of N protein is not involved in N-L interactions. Elucidating the fundamental processes that involve the nucleocapsid protein will add to our understanding of this important viral protein and may influence future studies in the development of novel antiviral strategies.
Highlights
Rift Valley fever phlebovirus (RVFV) is a member of the Phlebovirus genus of the Phenuiviridae family of viruses, in the Bunyavirales order [1]
Re-analysis of RVFV nucleocapsid, a key protein within the RVFV replication cycle has led to the characterisation of previously unidentified conserved amino acids
Fourteen Phlebovirus nucleoprotein sequences available from Genbank were aligned (Fig 1) and conserved residues were identified between all phleboviruses, between phleboviruses thought to be transmitted by an insect vector or phleboviruses transmitted by ticks
Summary
RVFV is a member of the Phlebovirus genus of the Phenuiviridae family of viruses, in the Bunyavirales order [1]. The N proteins of viruses belonging to the Bunyavirales order have been shown to function to encapsidate the viral genome which protects the genetic information from harsh conditions found in the intracellular environment, such as RNase degradative enzymes [9]. This encapsidation function of the N protein and the formation of the viral RNP complex allow the binding of the RNA-dependent RNA-polymerase thereby allowing transcription and replication to take place. N protein forms multimeric structures in infected cells [10,11,12]; in the case of RVFV the binding of the N-terminal arm to adjacent N monomers results in the formation of ring-shaped oligomers and allows the creation of filamentous RNPs required for replication of the viral genome [10]
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