Mechanistic insight into the efficient packaging of antigenomic S RNA into Rift Valley fever virus particles

 The infectious Rift Valley fever virus (RVFV) particle is packaged with L, M and S RNAs, in addition to their antigenomic RNA counterparts, and two envelope glycoproteins, Gn and Gc. The Gn and Gc glycoproteins are encoded in M segment and Gn is hypothesized to function as the matrix protein. The L segment encodes L protein. The S RNA uses ambisense coding strategy where the nucleocapsid and nonstructural mRNAs are transcribed from genomic S RNA and antigenomic S RNA respectively. Packaging of RVFV particle is associated with interaction between Gn and viral ribonucleoprotein complexes. However, Gn is reported to bind antigenomic S RNA efficiently compared to antigenomic L and M RNAs. This study characterized regions of viral RNA that directly interact with Gn using UV-crosslinking and immunoprecipitation followed by high-throughput sequencing. Multiple Gn-binding sites in genomic and antigenomic RVFV RNAs were identified. A prominent Gn-binding site was identified within 3’ noncoding region of the antigenomic S RNA. It was established that the prominent Gn-binding site has a significant role in effective packaging of antigenomic S RNA into virions. Therefore, immediately after viral infection, nonstructural proteins which are antagonist of interferon are synthesized and expressed, subsequently suppressing expression of interferon-β mRNA.

(LML)