The Polymerase-Associated Protein (M1) and the Matrix Protein (M2) from a Virulent and an Avirulent Strain of Viral Hemorrhagic Septicemia Virus (VHSV), a Fish Rhabdovirus

Virology ◽  
1994 ◽  
Vol 198 (2) ◽  
pp. 602-612 ◽  
Author(s):  
A. Benmansour ◽  
G. Paubert ◽  
J. Bernard ◽  
P. de Kinkelin
Keyword(s):  
Matrix Protein ◽  
Viral Hemorrhagic Septicemia Virus ◽  
Avirulent Strain ◽  
Viral Hemorrhagic Septicemia ◽  
The Matrix

scholarly journals The Nucleoprotein and Phosphoprotein Are Major Determinants of the Virulence of Viral Hemorrhagic Septicemia Virus in Rainbow Trout

2019 ◽  
Vol 93 (18) ◽  
Author(s):  
Vikram N. Vakharia ◽  
Jie Li ◽  
Douglas G. McKenney ◽  
Gael Kurath
Keyword(s):  
Rainbow Trout ◽  
Matrix Protein ◽  
Virulent Strain ◽  
N Gene ◽  
Viral Hemorrhagic Septicemia Virus ◽  
Avirulent Strain ◽  
Viral Hemorrhagic Septicemia ◽  
High Virulence ◽  
Specific Virulence ◽  
Host Component

ABSTRACTViral hemorrhagic septicemia virus (VHSV), a fish rhabdovirus, infects several marine and freshwater fish species. There are many strains of VHSV that affect different fish, but some strains of one genetic subgroup have gained high virulence in rainbow trout (Oncorhynchus mykiss). To define the genetic basis of high virulence in trout, we used reverse genetics to create chimeric VHSVs in which viral nucleoprotein (N), P (phosphoprotein), or M (matrix protein) genes, or the N and P genes, were exchanged between a trout-virulent European VHSV strain (DK-3592B) and a trout-avirulent North American VHSV strain (MI03). Testing of the chimeric recombinant VHSV (rVHSV) by intraperitoneal injection in juvenile rainbow trout showed that exchanges of the viral P or M genes had no effect on the trout virulence phenotype of either parental strain. However, reciprocal exchanges of the viral N gene resulted in a partial gain of function in the chimeric trout-avirulent strain (22% mortality) and complete loss of virulence for the chimeric trout-virulent strain (2% mortality). Reciprocal exchanges of both the N and P genes together resulted in complete gain of function in the chimeric avirulent strain (82% mortality), again with complete loss of virulence in the chimeric trout-virulent strain (0% mortality). Thus, the VHSV N gene contains an essential determinant of trout virulence that is strongly enhanced by the viral P gene. We hypothesize that the host-specific virulence mechanism may involve increased efficiency of the viral polymerase complex when the N and P proteins have adapted to more efficient interaction with a host component from rainbow trout.IMPORTANCERainbow trout farming is a major food source industry worldwide that has suffered great economic losses due to host jumps of fish rhabdovirus pathogens, followed by evolution of dramatic increases in trout-specific virulence. However, the genetic determinants of host jumps and increased virulence in rainbow trout are unknown for any fish rhabdovirus. Previous attempts to identify the viral genes containing trout virulence determinants of viral hemorrhagic septicemia virus (VHSV) have not been successful. We show here that, somewhat surprisingly, the viral nucleocapsid (N) and phosphoprotein (P) genes together contain the determinants responsible for trout virulence in VHSV. This suggests a novel host-specific virulence mechanism involving the viral polymerase and a host component. This differs from the known virulence mechanisms of mammalian rhabdoviruses based on the viral P or M (matrix) protein.

scholarly journals Role of Viral Hemorrhagic Septicemia Virus Matrix (M) Protein in Suppressing Host Transcription

2017 ◽  
Vol 91 (19) ◽  
Author(s):  
Qi Ke ◽  
Wade Weaver ◽  
Adam Pore ◽  
Bartolomeo Gorgoglione ◽  
Julia Halo Wildschutte ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Matrix Protein ◽  
Simian Virus 40 ◽  
Viral Hemorrhagic Septicemia Virus ◽  
Type I ◽  
Dependent Manner ◽  
Gene Promoters ◽  
Viral Hemorrhagic Septicemia ◽  
Rnap Ii

ABSTRACT Viral hemorrhagic septicemia virus (VHSV) is a pathogenic fish rhabdovirus found in discrete locales throughout the Northern Hemisphere. VHSV infection of fish cells leads to upregulation of the host's virus detection response, but the virus quickly suppresses interferon (IFN) production and antiviral gene expression. By systematically screening each of the six VHSV structural and nonstructural genes, we identified matrix protein (M) as the virus' most potent antihost protein. Only M of VHSV genotype IV sublineage b (VHSV-IVb) suppressed mitochondrial antiviral signaling protein (MAVS) and type I IFN-induced gene expression in a dose-dependent manner. M also suppressed the constitutively active simian virus 40 (SV40) promoter and globally decreased cellular RNA levels. Chromatin immunoprecipitation (ChIP) studies illustrated that M inhibited RNA polymerase II (RNAP II) recruitment to gene promoters and decreased RNAP II C-terminal domain (CTD) Ser2 phosphorylation during VHSV infection. However, transcription directed by RNAP I to III was suppressed by M. To identify regions of functional importance, M proteins from a variety of VHSV strains were tested in cell-based transcriptional inhibition assays. M of a particular VHSV-Ia strain, F1, was significantly less potent than IVb M at inhibiting SV40/luciferase (Luc) expression yet differed by just 4 amino acids. Mutation of D62 to alanine alone, or in combination with an E181-to-alanine mutation (D62A E181A), dramatically reduced the ability of IVb M to suppress host transcription. Introducing either M D62A or D62A E181A mutations into VHSV-IVb via reverse genetics resulted in viruses that replicated efficiently but exhibited less cytotoxicity and reduced antitranscriptional activities, implicating M as a primary regulator of cytopathicity and host transcriptional suppression. IMPORTANCE Viruses must suppress host antiviral responses to replicate and spread between hosts. In these studies, we identified the matrix protein of the deadly fish novirhabdovirus VHSV as a critical mediator of host suppression during infection. Our studies indicated that M alone could block cellular gene expression at very low expression levels. We identified several subtle mutations in M that were less potent at suppressing host transcription. When these mutations were engineered back into recombinant viruses, the resulting viruses replicated well but elicited less toxicity in infected cells and activated host innate immune responses more robustly. These data demonstrated that VHSV M plays an important role in mediating both virus-induced cell toxicity and viral replication. Our data suggest that its roles in these two processes can be separated to design effective attenuated viruses for vaccine candidates.

scholarly journals Heterologous Exchanges of the Glycoprotein and the Matrix Protein in a Novirhabdovirus

2002 ◽  
Vol 76 (6) ◽  
pp. 2881-2889 ◽  
Author(s):  
Stéphane Biacchesi ◽  
Monique Béarzotti ◽  
Edwige Bouguyon ◽  
Michel Brémont
Keyword(s):  
Matrix Protein ◽  
Genetic System ◽  
Amino Acid Identity ◽  
Reverse Genetic System ◽  
Viral Hemorrhagic Septicemia Virus ◽  
M Gene ◽  
Recombinant Viruses ◽  
Glycoprotein G ◽  
The Matrix ◽  
Infectious Hematopoietic Necrosis

ABSTRACT Infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV) are two salmonid rhabdoviruses replicating at low temperatures (14 to 20°C). Both viruses belong to the Novirhabdovirus genus, but they are only distantly related and do not cross antigenically. By using a recently developed reverse-genetic system based on IHNV (S. Biacchesi et al., J. Virol. 74:11247-11253, 2000), we investigated the ability to exchange IHNV glycoprotein G with that of VHSV. Thus, the IHNV genome was modified so that the VHSV G gene replaced the complete IHNV G gene. A recombinant virus expressing VHSV G instead of IHNV G, rIHNV-Gvhsv, was generated and was shown to replicate as well as the wild-type rIHNV in cell culture. This study was extended by exchanging IHNV G with that of a fish vesiculovirus able to replicate at high temperatures (up to 28°C), the spring viremia of carp virus (SVCV). rIHNV-Gsvcv was successfully recovered; however, its growth was restricted to 14 to 20°C. These results show the nonspecific sequence requirement for the insertion of heterologous glycoproteins into IHNV virions and also demonstrate that an IHNV protein other than the G protein is responsible for the low-temperature restriction on growth. To determine to what extent the matrix (M) protein interacts with G, a series of chimeric pIHNV constructs in which all or part of the M gene was replaced with the VHSV counterpart was engineered and used to recover the respective recombinant viruses. Despite the very low percentage (38%) of amino acid identity between the IHNV and VHSV matrix proteins, viable chimeric IHNVs, harboring either the matrix protein or both the glycoprotein and the matrix protein from VHSV, were recovered and propagated. Altogether, these data show the extreme flexibility of IHNV to accommodate heterologous structural proteins.

Periodic Structure in the Matrix Protein of an Insect Virus

1982 ◽  
Vol 40 ◽  
pp. 302-303
Author(s):  
H.M. Mazzone ◽  
W.F. Engler ◽  
R. Zerillo ◽  
G.F. Bahr
Keyword(s):  
Inclusion Body ◽  
Periodic Structure ◽  
Matrix Protein ◽  
Malacosoma Disstria ◽  
Insect Virus ◽  
Virus Particles ◽  
The Matrix ◽  
Nucleopolyhedrosis Virus

The nucleopolyhedrosis virus (NPV) of the forest tent cater - pillar (Malacosoma disstria Hubner) has been analyzed in our laboratories. As a representative of the Baculovirus class, the NPV has virus particles enclosed with in a proteinaceous structure, the inclusion body.

Complete sequences of 4 viral hemorrhagic septicemia virus IVb isolates and their virulence in northern pike fry

2017 ◽  
Vol 126 (3) ◽  
pp. 211-227 ◽  
Author(s):  
RG Getchell ◽  
ER Cornwell ◽  
S Bogdanowicz ◽  
J Andrés ◽  
WN Batts ◽  
...  
Keyword(s):  
Northern Pike ◽  
Viral Hemorrhagic Septicemia Virus ◽  
Viral Hemorrhagic Septicemia ◽  
Complete Sequences

scholarly journals Bacillus subtilis Inhibits Viral Hemorrhagic Septicemia Virus Infection in Olive Flounder (Paralichthys olivaceus) Intestinal Epithelial Cells

Viruses ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 28
Author(s):  
So-Ri Han ◽  
Hetron M. Munang’andu ◽  
In-Kyu Yeo ◽  
Sung-Hyun Kim
Keyword(s):  
Epithelial Cells ◽  
Viral Infections ◽  
Intestinal Epithelial Cells ◽  
Virus Entry ◽  
Paralichthys Olivaceus ◽  
Viral Hemorrhagic Septicemia Virus ◽  
Intestinal Epithelial ◽  
Internal Organs ◽  
Viral Hemorrhagic Septicemia ◽  
Olive Flounder Paralichthys Olivaceus

Viral hemorrhagic septicemia virus (VHSV) is a highly pathogenic virus that infects a wide range of host fish species causing high economic losses in aquaculture. Epithelial cells in mucosal organs are target sites for VHSV entry into fish. To protect fish against VHSV infection, there is a need to develop antiviral compounds able to prevent establishment of infection at portals of virus entry into fish. Bacillus subtilis is a probiotic with excellent antiviral properties, of which one of its secretions, surfactin, has been shown to inhibit viral infections in mammals. Herein, we demonstrate its ability to prevent VHSV infection in olive flounder (Paralichthys olivaceus) intestinal epithelial cells (IECs) and infection in internal organs. Our findings show inhibition of VHSV infection in IECs by B. subtilis and surfactin. In addition, our findings showed inhibition of VHSV in Epithelioma Papulosum Cyprini (EPC) cells inoculated with intestinal homogenates from the fish pretreated with B. subtilis by oral exposure, while the untreated fish had cytopathic effects (CPE) caused by VHSV infection in the intestines at 48 h after the VHSV challenge. At 96 h post-challenge, samples from the untreated fish had CPE from head kidney and spleen homogenates and no CPE were observed in the intestinal homogenates, while the B. subtilis-pretreated fish had no CPE in all organs. These findings demonstrate that inhibition of VHSV infection at portals of virus entry in the intestines culminated in prevention of infection in internal organs. In summary, our results show that B. subtilis has the potential to prevent VHSV infection in fish and that its use as a probiotic in aquaculture has the potential to serve as an antiviral therapeutic agent against different viral infections.

scholarly journals Characterization of Mmp37p, aSaccharomyces cerevisiaeMitochondrial Matrix Protein with a Role in Mitochondrial Protein Import

2006 ◽  
Vol 17 (9) ◽  
pp. 4051-4062 ◽  
Author(s):  
Michelle R. Gallas ◽  
Mary K. Dienhart ◽  
Rosemary A. Stuart ◽  
Roy M. Long
Keyword(s):  
Matrix Protein ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Temperature Sensitive ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Close Proximity ◽  
The Matrix ◽  
Targeting Signal

Many mitochondrial proteins are encoded by nuclear genes and after translation in the cytoplasm are imported via translocases in the outer and inner membranes, the TOM and TIM complexes, respectively. Here, we report the characterization of the mitochondrial protein, Mmp37p (YGR046w) and demonstrate its involvement in the process of protein import into mitochondria. Haploid cells deleted of MMP37 are viable but display a temperature-sensitive growth phenotype and are inviable in the absence of mitochondrial DNA. Mmp37p is located in the mitochondrial matrix where it is peripherally associated with the inner membrane. We show that Mmp37p has a role in the translocation of proteins across the mitochondrial inner membrane via the TIM23-PAM complex and further demonstrate that substrates containing a tightly folded domain in close proximity to their mitochondrial targeting sequences display a particular dependency on Mmp37p for mitochondrial import. Prior unfolding of the preprotein, or extension of the region between the targeting signal and the tightly folded domain, relieves their dependency for Mmp37p. Furthermore, evidence is presented to show that Mmp37 may affect the assembly state of the TIM23 complex. On the basis of these findings, we hypothesize that the presence of Mmp37p enhances the early stages of the TIM23 matrix import pathway to ensure engagement of incoming preproteins with the mtHsp70p/PAM complex, a step that is necessary to drive the unfolding and complete translocation of the preprotein into the matrix.

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