Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A single amino acid change in the C-terminal domain of the matrix protein M1 of influenza B virus confers mouse adaptation and virulence.

ABSTRACT: Serial passage of an initially avirulent influenza B virus, B/Memphis/12/97, resulted in the selection of a variant which was lethal in mice. Virulence correlated with improved growth in vivo and prolonged replication. Sequencing of the complete coding regions of the parent and mouse-adapted viruses revealed 8 amino acid differences. Sequencing and characterization of intermediate passages suggested that one change in the C-terminal domain of the M1 protein, an asparagine to a serine at position 221, was responsible for acquisition of virulence and lethality. Site-directed mutagenesis of the M segment of a different virus, B/Yamanashi/166/98, to change this amino acid residue confirmed its importance by conferring improved growth and virulence in mice. This observation suggests a role for the C domain of the M1 protein in growth and virulence in a mammalian host.

SUBMITTER: McCullers JA

PROVIDER: S-EPMC2737340 | biostudies-literature | 2005 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A single amino acid change in the C-terminal domain of the matrix protein M1 of influenza B virus confers mouse adaptation and virulence.

McCullers Jonathan A JA Hoffmann Erich E Huber Victor C VC Nickerson Asia D AD

Virology 20050601 2

Serial passage of an initially avirulent influenza B virus, B/Memphis/12/97, resulted in the selection of a variant which was lethal in mice. Virulence correlated with improved growth in vivo and prolonged replication. Sequencing of the complete coding regions of the parent and mouse-adapted viruses revealed 8 amino acid differences. Sequencing and characterization of intermediate passages suggested that one change in the C-terminal domain of the M1 protein, an asparagine to a serine at position ...[more]

PMID: 15892972

Similar Datasets

Dissection of influenza A virus M1 protein: pH-dependent oligomerization of N-terminal domain and dimerization of C-terminal domain.

Project description:BackgroundThe matrix 1 (M1) protein of Influenza A virus plays many critical roles throughout the virus life cycle. The oligomerization of M1 is essential for the formation of the viral matrix layer during the assembly and budding process.Methodology/principal findingsIn the present study, we report that M1 can oligomerize in vitro, and that the oligomerization is pH-dependent. The N-terminal domain of M1 alone exists as multiple-order oligomers at pH 7.4, and the C-terminal domain alone forms an exclusively stable dimer. As a result, intact M1 can display different forms of oligomers and dimer is the smallest oligomerization state, at neutral pH. At pH 5.0, oligomers of the N-terminal domain completely dissociate into monomers, while the C-terminal domain remains in dimeric form. As a result, oligomers of intact M1 dissociate into a stable dimer at acidic pH.Conclusions/significanceOligomerization of M1 involves both the N- and C-terminal domains. The N-terminal domain determines the pH-dependent oligomerization characteristic, and C-terminal domain forms a stable dimer, which contributes to the dimerization of M1. The present study will help to unveil the mechanisms of influenza A virus assembly and uncoating process.

| S-EPMC3360003 | biostudies-literature

pH-induced conformational change of the influenza M2 protein C-terminal domain.

Project description:The M2 protein from influenza A is a pH-activated proton channel that plays an essential role in the viral life cycle and serves as a drug target. Using spin labeling EPR spectroscopy, we studied a 38-residue M2 peptide spanning the transmembrane region and its C-terminal extension. We obtained residue-specific environmental parameters under both high- and low-pH conditions for nine consecutive C-terminal sites. The region forms a membrane surface helix at both high and low pH, although the arrangement of the monomers within the tetramer changes with pH. Both electrophysiology and EPR data point to a critical role for residue Lys 49.

| S-EPMC2746938 | biostudies-other

Amino acid substitutions V63I or A37S/I61T/V63I/V100A in the PA N-terminal domain increase the virulence of H7N7 influenza A virus.

Project description:The PA N-terminal domain (PA-Nter) is essential for viral transcription and replication. Here we identified PA-Nter substitutions A37S, I61T, V63I and V100A in recently emerged avian influenza A viruses (IAVs) with potential effect on virus pathogenicity and/or host adaptation. We introduced the identified PA-Nter substitutions into avian H7N7 IAV by reverse genetics. Our results showed that single substitution V63I and combined substitutions, I61T/V63I and A37S/I61T/V63I/V100A (Mfour), significantly increased virus growth capacity in mammalian cells. Meanwhile, these substitutions conferred higher virus transcription/replication capacity by producing more mRNA, cRNA and vRNA. Consistently, the polymerase activity and the endonuclease activity were enhanced by these PA-Nter substitutions. Notably, substitutions V63I and Mfour strongly increased virus replication and virulence in mice. Collectively, our findings demonstrated that the PA-Nter substitutions V63I and Mfour enhanced IAV pathogenicity through modification of the polymerase activity and the endonuclease activity, which added to the evolving knowledge of IAV virulence determinants.

| S-EPMC5122915 | biostudies-literature

Influenza A matrix protein M1 multimerizes upon binding to lipid membranes.

Project description:The matrix protein M1 plays a pivotal role in the budding of influenza virus from the plasma membrane (PM) of infected cells. This protein interacts with viral genetic material and envelope proteins while binding to the inner leaflet of the PM. Its oligomerization is therefore closely connected to the assembly of viral components and the formation of new virions. Of interest, the molecular details of M1 interaction with lipids and other viral proteins are far from being understood, and it remains to be determined whether the multimerization of M1 is affected by its binding to the PM and interaction with its components. To clarify the connection between M1 oligomerization and binding to lipid membranes, we applied a combination of several quantitative microscopy approaches. First, we used number and brightness (N&B) microscopy to characterize protein multimerization upon interaction with the PM of living cells. Second, we used controlled biophysical models of the PM (i.e., supported bilayers) to delve into the details of M1-lipid and M1-M1 interactions by employing a combination of raster image correlation spectroscopy (RICS), fluorescence correlation spectroscopy (FCS), and atomic force microscopy (AFM). Our results show that M1 oligomer formation is strongly enhanced by membrane binding and does not necessarily require the presence of other viral proteins. Furthermore, we propose a specific model to explain M1 binding to the lipid bilayer and the formation of multimers.

| S-EPMC4142230 | biostudies-other

A crucial role of N-terminal domain of influenza A virus M1 protein in interaction with swine importin ?1 protein.

Project description:The matrix 1 (M1) protein is a multifunctional protein in the life cycle of influenza virus. It plays an important role in virus budding and intracellular trafficking of viral ribonucleoproteins (vRNPs). The M1 protein consists of three domains based on the structure: N-terminal domain, Middle domain, and C-terminal domain. However, the functions of different domains of the M1 protein remain largely unclear. In this study, using bimolecular fluorescence complementation assays (BIFC) we demonstrated that swine importin ?1 interacts with the M1 protein and transports it to the nucleus. Interestingly, M1 with mutated nuclear localization signal (NLS; 101-RKLKR-105 to 101-AALAA-105) still interacts with swine importin ?1 and is localized in the nucleus, suggesting that the NLS located at residues 101-105 is not the only NLS within M1 recombinant protein containing 1-160 residues of M1 with mutated nuclear localization signal is able to interact with swine importin ?1, but M1/60-252 domains cannot bind importin ?1. Further mapping showed that the deletion of residues 1-20 impaired the interaction between N terminus of M1 and importin ?1. Collectively, our data suggested that the N-terminal domain of M1 protein is critical for binding swine importin ?1 and for nuclear localization.

| S-EPMC4111955 | biostudies-literature

Crystal structures of influenza A virus matrix protein M1: variations on a theme.

Project description:Matrix protein 1 (M1) of the influenza A virus plays multiple roles in virion assembly and infection. Interest in the pH dependence of M1's multiple functions led us to study the effect of subtle pH changes on M1 structure, resulting in the elucidation of a unique low-pH crystal structure of the N(1-165)-domain of A/WSN/33 (H1N1) M1 that has never been reported. Although the 2.2 Å crystal structure of M1 N-terminus shows a dimer with the two monomers interacting in a face-to-face fashion at low pH as observed earlier, a 44° rotation of the second monomer has led to a significantly different dimer interface that possibly affects dimer stability. More importantly, while one of the monomers is fully defined, the N-terminal half of the second monomer shows considerable disorder that appears inherent in the protein and is potentially physiologically relevant. Such disorder has not been observed in any other previously reported structure at either low or high pH conditions, despite similar crystallization pH conditions. By comparing our novel N(1-165)-domain structure with other low-pH or neutral-pH M1 structures, it appears that M1 can energetically access different monomer and dimer conformations, as well as oligomeric states, with varying degree of similarities. The study reported here provides further insights into M1 oligomerization that may be essential for viral propagation and infectivity.

| S-EPMC4190115 | biostudies-literature

Truncation of C-terminal 20 amino acids in PA-X contributes to adaptation of swine influenza virus in pigs.

Project description:The PA-X protein is a fusion protein incorporating the N-terminal 191 amino acids of the PA protein with a short C-terminal sequence encoded by an overlapping ORF (X-ORF) in segment 3 that is accessed by + 1 ribosomal frameshifting, and this X-ORF exists in either full length or a truncated form (either 61-or 41-condons). Genetic evolution analysis indicates that all swine influenza viruses (SIVs) possessed full-length PA-X prior to 1985, but since then SIVs with truncated PA-X have gradually increased and become dominant, implying that truncation of this protein may contribute to the adaptation of influenza virus in pigs. To verify this hypothesis, we constructed PA-X extended viruses in the background of a "triple-reassortment" H1N2 SIV with truncated PA-X, and evaluated their biological characteristics in vitro and in vivo. Compared with full-length PA-X, SIV with truncated PA-X had increased viral replication in porcine cells and swine respiratory tissues, along with enhanced pathogenicity, replication and transmissibility in pigs. Furthermore, we found that truncation of PA-X improved the inhibition of IFN-I mRNA expression. Hereby, our results imply that truncation of PA-X may contribute to the adaptation of SIV in pigs.

| S-EPMC4766433 | biostudies-other

A single amino acid change within antigenic domain II of the spike protein of bovine coronavirus confers resistance to virus neutralization.

Project description:The spike glycoprotein is a major neutralizing antigen of bovine coronavirus (BCV). Conformational neutralizing epitopes of group A and group B monoclonal antibodies (MAbs) have previously been mapped to two domains at amino acids 351 to 403 (domain I) and amino acids 517 to 621 (domain II). To further map antigenic sites, neutralization escape mutants of BCV were selected with a group A MAb which has both in vitro and in vivo virus-neutralizing ability. The escape mutants were demonstrated to be neutralization resistant to the selecting group A MAb and remained sensitive to neutralization by a group B MAb. In radioimmunoprecipitation assays, the spike proteins of neutralization escape mutants were shown to have lost their reactivities with the selecting group A MAb. Sequence analysis of the spike protein genes of the escape mutants identified a single nucleotide substitution of C to T at position 1583, resulting in the change of alanine to valine at amino acid position 528 (A528V). The mutation occurs in domain II and in a location which corresponds to the hypervariable region of the spike protein of the coronavirus mouse hepatitis virus. Experimental introduction of the A528V mutation into the wild-type spike protein resulted in the loss of MAb binding of the mutant protein, confirming that the single point mutation was responsible for the escape of BCV from immunological selective pressure.

| S-EPMC96053 | biostudies-literature

BRCA2 C-Terminal RAD51-Binding Domain Confers Resistance to DNA-Damaging Agents.

Project description:Breast cancer type 2 susceptibility (BRCA2) protein is crucial for initiating DNA damage repair after chemotherapy with DNA interstrand crosslinking agents or X-ray irradiation, which induces DNA double-strand breaks. BRCA2 contains a C-terminal RAD51-binding domain (CTRBD) that interacts with RAD51 oligomer-containing nucleofilaments. In this study, we investigated CTRBD expression in cells exposed to X-ray irradiation and mitomycin C treatment. Surprisingly, BRCA2 CTRBD expression in HeLa cells increased their resistance to X-ray irradiation and mitomycin C. Under endogenous BRCA2 depletion using shRNA, the sensitivities of the BRCA2-depleted cells with and without the CTRBD did not significantly differ. Thus, the resistance to X-ray irradiation conferred by an exogenous CTRBD required endogenous BRCA2 expression. BRCA2 CTRBD-expressing cells demonstrated effective RAD51 foci formation and increased homologous recombination efficiency, but not nonhomologous end-joining efficiency. To the best of our knowledge, our study is the first to report the ability of the BRCA2 functional domain to confer resistance to X-ray irradiation and mitomycin C treatment by increased homologous recombination efficiency. Thus, this peptide may be useful for protecting cells against X-ray irradiation or chemotherapeutic agents.

| S-EPMC9000072 | biostudies-literature

The C-terminal domain of the virulence factor MgtC is a divergent ACT domain.

Project description:MgtC is a virulence factor of unknown function important for survival inside macrophages in several intracellular bacterial pathogens, including Mycobacterium tuberculosis. It is also involved in adaptation to Mg(2+) deprivation, but previous work suggested that MgtC is not a Mg(2+) transporter. In this study, we demonstrated that the amount of the M. tuberculosis MgtC protein is not significantly increased by Mg(2+) deprivation. Members of the MgtC protein family share a conserved membrane N-terminal domain and a more divergent cytoplasmic C-terminal domain. To get insights into MgtC functional and structural organization, we have determined the nuclear magnetic resonance (NMR) structure of the C-terminal domain of M. tuberculosis MgtC. This structure is not affected by the Mg(2+) concentration, indicating that it does not bind Mg(2+). The structure of the C-terminal domain forms a ?????? fold found in small molecule binding domains called ACT domains. However, the M. tuberculosis MgtC ACT domain differs from canonical ACT domains because it appears to lack the ability to dimerize and to bind small molecules. We have shown, using a bacterial two-hybrid system, that the M. tuberculosis MgtC protein can dimerize and that the C-terminal domain somehow facilitates this dimerization. Taken together, these results indicate that M. tuberculosis MgtC does not have an intrinsic function related to Mg(2+) uptake or binding but could act as a regulatory factor based on protein-protein interaction that could be facilitated by its ACT domain.

| S-EPMC3486350 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data