The Central Role of the Matrix Protein in Nipah Virus Assembly and Morphogenesis

2007 ◽  
Author(s):  
Jared R. Patch
Keyword(s):  
Matrix Protein ◽  
Virus Assembly ◽  
Nipah Virus ◽  
The Matrix

scholarly journals Intergenotypic Replacement of Lyssavirus Matrix Proteins Demonstrates the Role of Lyssavirus M Proteins in Intracellular Virus Accumulation

2009 ◽  
Vol 84 (4) ◽  
pp. 1816-1827 ◽  
Author(s):  
Stefan Finke ◽  
Harald Granzow ◽  
Jose Hurst ◽  
Reiko Pollin ◽  
Thomas C. Mettenleiter
Keyword(s):  
Endoplasmic Reticulum ◽  
Matrix Protein ◽  
Virus Assembly ◽  
Virus Release ◽  
Host Tropism ◽  
Adaptive Mutations ◽  
M Proteins ◽  
The Matrix ◽  
Virus Genomes

ABSTRACT Lyssavirus assembly depends on the matrix protein (M). We compared lyssavirus M proteins from different genotypes for their ability to support assembly and egress of genotype 1 rabies virus (RABV). Transcomplementation of M-deficient RABV with M from European bat lyssavirus (EBLV) types 1 and 2 reduced the release of infectious virus. Stable introduction of the heterogenotypic M proteins into RABV led to chimeric viruses with reduced virus release and intracellular accumulation of virus genomes. Although the chimeras indicated genotype-specific evolution of M, rapid selection of a compensatory mutant suggested conserved mechanisms of lyssavirus assembly and the requirement for only few adaptive mutations to fit the heterogenotypic M to a RABV backbone. Whereas the compensatory mutant replicated to similar infectious titers as RABV M-expressing virus, ultrastructural analysis revealed that both nonadapted EBLV M chimeras and the compensatory mutant differed from RABV M expressing viruses in the lack of intracellular viruslike structures that are enveloped and accumulate in cisterna of the degranulated and dilated rough endoplasmic reticulum compartment. Moreover, all viruses were able to bud at the plasma membrane. Since the lack of the intracellular viruslike structures correlated with the type of M protein but not with the efficiency of virus release, we hypothesize that the M proteins of EBLV-1 and RABV differ in their target membranes for virus assembly. Although the biological function of intracellular assembly and accumulation of viruslike structures in the endoplasmic reticulum remain unclear, the observed differences could contribute to diverse host tropism or pathogenicity.

scholarly journals Nipah Virus Matrix Protein Influences Fusogenicity and Is Essential for Particle Infectivity and Stability

2015 ◽  
Vol 90 (5) ◽  
pp. 2514-2522 ◽  
Author(s):  
Erik Dietzel ◽  
Larissa Kolesnikova ◽  
Bevan Sawatsky ◽  
Anja Heiner ◽  
Michael Weis ◽  
...  
Keyword(s):  
Life Cycle ◽  
Cell Fusion ◽  
Matrix Protein ◽  
Fluorescent Protein ◽  
Critical Role ◽  
Nipah Virus ◽  
M Protein ◽  
The Matrix ◽  
Cell Cell

ABSTRACTNipah virus (NiV) causes fatal encephalitic infections in humans. To characterize the role of the matrix (M) protein in the viral life cycle, we generated a reverse genetics system based on NiV strain Malaysia. Using an enhanced green fluorescent protein (eGFP)-expressing M protein-deleted NiV, we observed a slightly increased cell-cell fusion, slow replication kinetics, and significantly reduced peak titers compared to the parental virus. While increased amounts of viral proteins were found in the supernatant of cells infected with M-deleted NiV, the infectivity-to-particle ratio was more than 100-fold reduced, and the particles were less thermostable and of more irregular morphology. Taken together, our data demonstrate that the M protein is not absolutely required for the production of cell-free NiV but is necessary for proper assembly and release of stable infectious NiV particles.IMPORTANCEHenipaviruses cause a severe disease with high mortality in human patients. Therefore, these viruses can be studied only in biosafety level 4 (BSL-4) laboratories, making it more challenging to characterize their life cycle. Here we investigated the role of the Nipah virus matrix protein in virus-mediated cell-cell fusion and in the formation and release of newly produced particles. We found that even though low levels of infectious viruses are produced in the absence of the matrix protein, it is required for the release of highly infectious and stable particles. Fusogenicity of matrixless viruses was slightly enhanced, further demonstrating the critical role of this protein in different steps of Nipah virus spread.

scholarly journals The Matrix Protein of Nipah Virus Targets the E3-Ubiquitin Ligase TRIM6 to Inhibit the IKKε Kinase-Mediated Type-I IFN Antiviral Response

2016 ◽  
Vol 12 (9) ◽  
pp. e1005880 ◽  
Author(s):  
Preeti Bharaj ◽  
Yao E. Wang ◽  
Brian E. Dawes ◽  
Tatyana E. Yun ◽  
Arnold Park ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Matrix Protein ◽  
Nipah Virus ◽  
E3 Ubiquitin Ligase ◽  
Antiviral Response ◽  
Type I ◽  
Type I Ifn ◽  
The Matrix

scholarly journals Influenza Virus Matrix Protein Is the Major Driving Force in Virus Budding

2000 ◽  
Vol 74 (24) ◽  
pp. 11538-11547 ◽  
Author(s):  
Paulino Gómez-Puertas ◽  
Carmen Albo ◽  
Esperanza Pérez-Pastrana ◽  
Amparo Vivo ◽  
Agustı́n Portela
Keyword(s):  
Virus Particle ◽  
Influenza A ◽  
Matrix Protein ◽  
Virus Assembly ◽  
Microscopic Analysis ◽  
Tubular Structures ◽  
Electron Microscopic ◽  
Particle Assembly ◽  
M1 Protein ◽  
The Matrix

ABSTRACT To get insights into the role played by each of the influenza A virus polypeptides in morphogenesis and virus particle assembly, the generation of virus-like particles (VLPs) has been examined in COS-1 cell cultures expressing, from recombinant plasmids, different combinations of the viral structural proteins. The presence of VLPs was examined biochemically, following centrifugation of the supernatants collected from transfected cells through sucrose cushions and immunoblotting, and by electron-microscopic analysis. It is demonstrated that the matrix (M1) protein is the only viral component which is essential for VLP formation and that the viral ribonucleoproteins are not required for virus particle formation. It is also shown that the M1 protein, when expressed alone, assembles into virus-like budding particles, which are released in the culture medium, and that the recombinant M1 protein accumulates intracellularly, forming tubular structures. All these results are discussed with regard to the roles played by the virus polypeptides during virus assembly.

scholarly journals SIRT1 activity orchestrates ECM expression during hESC-chondrogenic differentiation

2020 ◽  
Author(s):  
Christopher A Smith ◽  
Paul A Humphreys ◽  
Nicola Bates ◽  
Mark A Naven ◽  
Stuart A Cain ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Cell Function ◽  
Epigenetic Modification ◽  
Embryonic Stem ◽  
Type Ii Collagen ◽  
Cartilage Development ◽  
The Matrix ◽  
Col2a1 Expression ◽  
Key Driver

AbstractEpigenetic modification is a key driver of differentiation and the deacetylase Sirtuin1 (SIRT1) is an established regulator of cell function, ageing and articular cartilage homeostasis. Here we investigate the role of SIRT1 during development of chondrocytes by using human embryonic stem cells (hESCs). HESC-chondroprogenitors were treated with SIRT1 activator; SRT1720, or inhibitor; EX527, at different development stages. Activation of SIRT1 during 3D-pellet culture led to significant increases in expression of ECM genes for type-II collagen (COL2A1) and aggrecan (ACAN), and chondrogenic transcription factors SOX5 and ARID5B, with SOX5 ChIP analysis demonstrating enrichment on the ACAN –10 enhancer. Unexpectedly, while ACAN was enhanced, GAG retention in the matrix was reduced when SIRT1 was activated. Significantly, ARID5B and COL2A1 were positively correlated, with Co-IP indicating association of ARID5B with SIRT1 suggesting that COL2A1 expression is promoted by an ARID5B and SIRT1 interaction. In conclusion, SIRT1 activation positively impacts on the expression of the main ECM proteins, whilst altering ECM composition and suppressing GAG content during cartilage development. These results suggest that SIRT1 activity can be beneficial to cartilage development and matrix protein synthesis but tailored by addition of other positive GAG mediators.

scholarly journals A Conserved Tryptophan in the Ebola Virus Matrix Protein C-Terminal Domain Is Required for Efficient Virus-Like Particle Formation

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 402 ◽  
Author(s):  
Kristen A. Johnson ◽  
Rudramani Pokhrel ◽  
Melissa R. Budicini ◽  
Bernard S. Gerstman ◽  
Prem P. Chapagain ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Membrane Localization ◽  
Virus Like Particles ◽  
Plasma Membrane Localization ◽  
The Matrix ◽  
Dynamics Simulations

The Ebola virus (EBOV) harbors seven genes, one of which is the matrix protein eVP40, a peripheral protein that is sufficient to induce the formation of virus-like particles from the host cell plasma membrane. eVP40 can form different structures to fulfil different functions during the viral life cycle, although the structural dynamics of eVP40 that warrant dimer, hexamer, and octamer formation are still poorly understood. eVP40 has two conserved Trp residues at positions 95 and 191. The role of Trp95 has been characterized in depth as it serves as an important residue in eVP40 oligomer formation. To gain insight into the functional role of Trp191 in eVP40, we prepared mutations of Trp191 (W191A or W191F) to determine the effects of mutation on eVP40 plasma membrane localization and budding as well as eVP40 oligomerization. These in vitro and cellular experiments were complemented by molecular dynamics simulations of the wild-type (WT) eVP40 structure versus that of W191A. Taken together, Trp is shown to be a critical amino acid at position 191 as mutation to Ala reduces the ability of VP40 to localize to the plasma membrane inner leaflet and form new virus-like particles. Further, mutation of Trp191 to Ala or Phe shifted the in vitro equilibrium to the octamer form by destabilizing Trp191 interactions with nearby residues. This study has shed new light on the importance of interdomain interactions in stability of the eVP40 structure and the critical nature of timing of eVP40 oligomerization for plasma membrane localization and viral budding.

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

2019 ◽  
Vol 221 (Supplement_4) ◽  
pp. S389-S394 ◽  
Author(s):  
Marc Ringel ◽  
Laura Behner ◽  
Anja Heiner ◽  
Lucie Sauerhering ◽  
Andrea Maisner
Keyword(s):  
Plasma Membrane ◽  
Nuclear Export ◽  
Matrix Protein ◽  
Virus Assembly ◽  
Nipah Virus ◽  
Nuclear Export Signal ◽  
Cell Types ◽  
Surface Transport ◽  
M Proteins ◽  
Infected Cells

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.

Production of the matrix protein of Nipah virus in Escherichia coli: Virus-like particles and possible application for diagnosis

2009 ◽  
Vol 162 (1-2) ◽  
pp. 179-183 ◽  
Author(s):  
Senthil Kumar Subramanian ◽  
Beng Ti Tey ◽  
Muhajir Hamid ◽  
Wen Siang Tan
Keyword(s):  
Escherichia Coli ◽  
Matrix Protein ◽  
Nipah Virus ◽  
Virus Like Particles ◽  
The Matrix

scholarly journals A Single Amino Acid Deletion in the Matrix Protein of Porcine Reproductive and Respiratory Syndrome Virus Confers Resistance to a Polyclonal Swine Antibody with Broadly Neutralizing Activity

2015 ◽  
Vol 89 (12) ◽  
pp. 6515-6520 ◽  
Author(s):  
Benjamin R. Trible ◽  
Luca N. Popescu ◽  
Nicholas Monday ◽  
Jay G. Calvert ◽  
Raymond R. R. Rowland
Keyword(s):  
Amino Acid ◽  
Matrix Protein ◽  
Infectious Clone ◽  
Virus Neutralization ◽  
Single Amino Acid ◽  
Respiratory Syndrome Virus ◽  
Amino Acid Deletion ◽  
Neutralizing Activity ◽  
The Matrix

Assessment of virus neutralization (VN) activity in 176 pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV) identified one pig with broadly neutralizing activity. A Tyr-10 deletion in the matrix protein provided escape from broad neutralization without affecting homologous neutralizing activity. The role of the Tyr-10 deletion was confirmed through an infectious clone with a Tyr-10 deletion. The results demonstrate differences in the properties and specificities of VN responses elicited during PRRSV infection.

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