Replication of a Nipah Virus Encoding a Nuclear-Retained Matrix Protein

Abstract

Nipah virus (NiV) matrix protein (NiV M) plays a major role in virus assembly. It undergoes nuclear transit before accumulating at the plasma membrane and recruiting nucleocapsids to the budding sites. Because nuclear NiV M cannot be detected in all cell types, we wondered whether it can reach the cell surface by bypassing the nucleus. Using an M mutant with a defective nuclear export signal (MNESmut), however, we revealed that the nuclear import of M is ubiquitous, because MNESmut was retained in the nuclei of all cell types tested. Because a functional nuclear transit is a general prerequisite for M surface transport, we wanted to characterize the effect of nuclear-retained M protein in a full viral context and generated a recombinant NiV-MNESmut. Mutant NiV-MNESmut caused increased cell-cell fusion and produced lower virus titers. As expected for an assembly defective NiV, perinuclear inclusions (IBperi) were formed, but inclusions at the plasma membrane (IBPM), which probably represent the viral assembly platforms, were not found. It is interesting to note that the transport-defective MNESmut was recruited to IBperi. This probably prevents overaccumulation of nonfunctional M proteins in the cytoplasm and nuclei of NiV-infected cells and thus provides first evidence that IBperi are functionally relevant aggresome-like compartments.

The Potential Role of the ZIKV NS5 Nuclear Spherical-Shell Structures in Cell Type-Specific Host Immune Modulation during ZIKV Infection

“…Nuclear export can also play a role in the subcellular localization of proteins as has been reported for several virus proteins [24,[49][50][51], including flavivirus NS5 which has a conserved nuclear export sequence (NES) ( Figure 1). But broader validation studies are needed to evaluate the functional role of nuclear export in flaviviruses, especially in the context of ZIKV NS5 which forms supramolecular spherical shell-like structures in the nucleus [21].…”

Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription

“…This mechanism of IFN inhibition has been described for measles virus nucleoprotein ( Takayama et al, 2012 ) and Ebola virus VP24 protein ( Xu et al, 2014 ). Other viral matrix proteins, including RSV and Nipah virus matrix, traffic through the nucleus as a prerequisite for virion assembly and budding; however, the biological significance of the nuclear shuttling of matrix remains unclear ( Coleman and Peeples, 1993 ; Günther et al, 2020 ; Pentecost et al, 2015 ; Ringel et al, 2020 ; Wang et al, 2010 ). Notably, nucleocytoplasmic trafficking of viral structural proteins is facilitated by nuclear localization signals (NLSs) and/or sequences enriched with lysine or arginine residues that can mimic NLSs ( Tessier et al, 2019 ; Yarbrough et al, 2014 ).…”

The Structural Features of Henipavirus Matrix Protein Driving Intracellular Trafficking

“…Nuclear export of M is also essential for viral assembly and budding, with L106/107A mutations (within the nuclear export signal) resulting in nuclear accumulation and failure of M to form inclusion bodies beneath the plasma membrane, a precursor to viral budding (56,69). Interaction and nuclear accumulation of HeV and NiV M with ANP32B, a CRM-1 nuclear export adaptor, were documented by Bauer et al (7) and ANP32B has been further established by Gunther et al (23) as a common nuclear target for paramyxoviral M proteins.…”