posted on 2023-12-17, 18:29authored byLennart Sänger, Harry M. Williams, Dingquan Yu, Dominik Vogel, Jan Kosinski, Maria Rosenthal, Charlotte Uetrecht
Lassa virus is a
negative-strand RNA virus with only four structural
proteins that causes periodic outbreaks in West Africa. The nucleoprotein
(NP) encapsidates the viral genome, forming ribonucleoprotein complexes
(RNPs) together with the viral RNA and the L protein. RNPs must be
continuously restructured during viral genome replication and transcription.
The Z protein is important for membrane recruitment of RNPs, viral
particle assembly, and budding and has also been shown to interact
with the L protein. However, the interaction of NP, viral RNA, and
Z is poorly understood. Here, we characterize the interactions between
Lassa virus NP, Z, and RNA using structural mass spectrometry. We
identify the presence of RNA as the driver for the disassembly of
ring-like NP trimers, a storage form, into monomers to subsequently
form higher order RNA-bound NP assemblies. We locate the interaction
site of Z and NP and demonstrate that while NP binds Z independently
of the presence of RNA, this interaction is pH-dependent. These data
improve our understanding of RNP assembly, recruitment, and release
in Lassa virus.