scholarly journals Phenotypic Divergence of P Proteins of Australian Bat Lyssavirus Lineages Circulating in Microbats and Flying Foxes

2021 ◽  
Author(s):  
Celine Deffrasnes ◽  
Meng-Xiao Luo ◽  
Linda Wiltzer ◽  
Cassandra T David ◽  
Kim G Lieu ◽  
...  
Keyword(s):  
Molecular Mapping ◽  
Protein A ◽  
Fine Tuning ◽  
Nuclear Trafficking ◽  
P Protein ◽  
Phenotypic Divergence ◽  
Reservoir Species ◽  
Pathogenic Viruses ◽  
P Proteins ◽  
Australian Bat Lyssavirus

Bats are reservoirs of many pathogenic viruses including the lyssaviruses rabies virus (RABV) and Australian bat lyssavirus (ABLV). Lyssavirus strains are closely associated with particular host reservoir species, with evidence of specific adaptation. Associated phenotypic changes remain poorly understood but are likely to involve P protein, a key mediator of the intracellular virus-host interface. Here, we examine the phenotype of P protein of ABLV, which circulates as two defined lineages associated with frugivorous and insectivorous bats, providing the opportunity compare proteins of viruses adapted to divergent bat species. We report that key functions of P protein in interferon/STAT1 antagonism and the capacity of P protein to undergo nuclear trafficking differ between lineages. Molecular mapping indicates that these differences are functionally distinct, and appear to involve modulatory effects on regulatory regions or structural impact, rather than changes to defined interaction sequences. This results in partial but significant phenotypic divergence, consistent with ‘fine-tuning’ to host biology, and with potentially distinct properties in the virus-host interface between bat families that represent key zoonotic reservoirs.

scholarly journals Study of the Assembly of Vesicular Stomatitis Virus N Protein: Role of the P Protein

2000 ◽  
Vol 74 (20) ◽  
pp. 9515-9524 ◽  
Author(s):  
Todd J. Green ◽  
Silvia Macpherson ◽  
Shihong Qiu ◽  
Jacob Lebowitz ◽  
Gail W. Wertz ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Analytical Ultracentrifugation ◽  
Structural Information ◽  
Protein Complexes ◽  
Outer Diameter ◽  
N Protein ◽  
Molar Ratios ◽  
P Protein ◽  
Vesicular Stomatitis ◽  
P Proteins

ABSTRACT To derive structural information about the vesicular stomatitis virus (VSV) nucleocapsid (N) protein, the N protein and the VSV phosphoprotein (P protein) were expressed together in Escherichia coli. The N and P proteins formed soluble protein complexes of various molar ratios when coexpressed. The major N/P protein complex was composed of 10 molecules of the N protein, 5 molecules of the P protein, and an RNA. A soluble N protein-RNA oligomer free of the P protein was isolated from the N/P protein-RNA complex using conditions of lowered pH. The molecular weight of the N protein-RNA oligomer, 513,879, as determined by analytical ultracentrifugation, showed that it was composed of 10 molecules of the N protein and an RNA of approximately 90 nucleotides. The N protein-RNA oligomer had the appearance of a disk with outer diameter, inner diameter, and thickness of 148 ± 10 Å, 78 ± 9 Å, and 83 ± 8 Å, respectively, as determined by electron microscopy. RNA in the complexes was protected from RNase digestion and was stable at pH 11. This verified that N/P protein complexes expressed in E. coli were competent for encapsidation. In addition to coexpression with the full-length P protein, the N protein was expressed with the C-terminal 72 amino acids of the P protein. This portion of the P protein was sufficient for binding to the N protein, maintaining it in a soluble state, and for assembly of N protein-RNA oligomers. With the results provided in this report, we propose a model for the assembly of an N/P protein-RNA oligomer.

scholarly journals p30 protein: a critical regulator of HTLV-1 viral latency and host immunity

Retrovirology ◽  
2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Ramona Moles ◽  
Sarkis Sarkis ◽  
Veronica Galli ◽  
Maria Omsland ◽  
Damian F. J. Purcell ◽  
...  
Keyword(s):  
T Cell ◽  
Viral Infection ◽  
Cell Transformation ◽  
Leukemia Virus ◽  
Single Point ◽  
Protein A ◽  
Indigenous Communities ◽  
Fine Tuning ◽  
Single Point Mutation ◽  
Subtype C

AbstractThe extraordinarily high prevalence of HTLV-1 subtype C (HTLV-1C) in some isolated indigenous communities in Oceania and the severity of the health conditions associated with the virus impress the great need for basic and translational research to prevent and treat HTLV-1 infection. The genome of the virus’s most common subtype, HTLV-1A, encodes structural, enzymatic, and regulatory proteins that contribute to viral persistence and pathogenesis. Among these is the p30 protein encoded by the doubly spliced Tax-orf II mRNA, a nuclear/nucleolar protein with both transcriptional and post-transcriptional activity. The p30 protein inhibits the productive replication cycle via nuclear retention of the mRNA that encodes for both the viral transcriptional trans-activator Tax, and the Rex proteins that regulate the transport of incompletely spliced viral mRNA to the cytoplasm. In myeloid cells, p30 inhibits the PU-1 transcription factor that regulates interferon expression and is a critical mediator of innate and adaptive immunity. Furthermore, p30 alters gene expression, cell cycle progression, and DNA damage responses in T-cells, raising the hypothesis that p30 may directly contribute to T cell transformation. By fine-tuning viral expression while also inhibiting host innate responses, p30 is likely essential for viral infection and persistence. This concept is supported by the finding that macaques, a natural host for the closely genetically related simian T-cell leukemia virus 1 (STLV-1), exposed to an HTLV-1 knockout for p30 expression by a single point mutation do not became infected unless reversion and selection of the wild type HTLV-1 genotype occurs. All together, these data suggest that inhibition of p30 may help to curb and eventually eradicate viral infection by exposing infected cells to an effective host immune response.

P-Protein: A Novel Target for Skin-whitening Agent

2019 ◽  
Vol 24 (1) ◽  
pp. 76-84
Author(s):  
Birendra Kumar Singh ◽  
Eun-Ki Kim
Keyword(s):  
Protein A ◽  
Skin Whitening ◽  
Whitening Agent ◽  
P Protein ◽  
Novel Target

scholarly journals Role of Sp1 in insulin regulation of gene expression

2002 ◽  
Vol 29 (3) ◽  
pp. 265-279 ◽  
Author(s):  
SL Samson ◽  
NC Wong
Keyword(s):  
Intracellular Signaling ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Protein A ◽  
Peptide Hormone ◽  
Fine Tuning ◽  
Signaling Cascades ◽  
Specific Interest ◽  
Extracellular Signals

Sp1 is a ubiquitous nuclear factor that plays a key role in maintaining basal transcription of 'house-keeping' genes. However, recent evidence points to a more important function for Sp1 in mediating 'cross-talk' between selected signaling cascades to regulate the target genes that respond to these pathways. The role of Sp1 in mediating the actions of the peptide hormone insulin is of specific interest and serves as a model for detailing effects of intracellular signaling on Sp1 activity. This review summarizes studies suggesting that changes in Sp1 phosphorylation provide one potential mechanism for manipulating activity of this protein. A growing body of evidence reveals that the DNA binding and transcription activity of Sp1 may increase or decrease in response to changes in phosphorylation. This enables 'fine-tuning' of Sp1 activity for regulation of gene transcription. Several mechanisms exist by which Sp1 alters gene activity in response to insulin. These include independent Sp1 activity as well as collaboration or competition with others factors. This review points to an ever-increasing role for Sp1 in regulating the transcription of genes in response to extracellular signals such as insulin.

scholarly journals Transcriptome Analysis of Alternative Splicing Events Induced by Arbuscular Mycorrhizal Fungi (Rhizophagus irregularis) in Pea (Pisum sativum L.) Roots

Plants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1700
Author(s):  
Evgeny A. Zorin ◽  
Alexey M. Afonin ◽  
Olga A. Kulaeva ◽  
Emma S. Gribchenko ◽  
Oksana Y. Shtark ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Pisum Sativum ◽  
Mycorrhizal Fungi ◽  
Intron Retention ◽  
Protein A ◽  
Fine Tuning ◽  
Mrna Isoforms ◽  
Pisum Sativum L ◽  
Mycorrhizal Roots

Alternative splicing (AS), a process that enables formation of different mRNA isoforms due to alternative ways of pre-mRNA processing, is one of the mechanisms for fine-tuning gene expression. Currently, the role of AS in symbioses formed by plants with soil microorganisms is not fully understood. In this work, a comprehensive analysis of the transcriptome of garden pea (Pisum sativum L.) roots in symbiosis with arbuscular mycorrhiza was performed using RNAseq and following bioinformatic analysis. AS profiles of mycorrhizal and control roots were highly similar, intron retention accounting for a large proportion of the observed AS types (67%). Using three different tools (SUPPA2, DRIMSeq and IsoformSwitchAnalyzeR), eight genes with AS events specific for mycorrhizal roots of pea were identified, among which four were annotated as encoding an apoptosis inhibitor protein, a serine/threonine-protein kinase, a dehydrodolichyl diphosphate synthase, and a pre-mRNA-splicing factor ATP-dependent RNA helicase DEAH1. In pea mycorrhizal roots, the isoforms of these four genes with preliminary stop codons leading to a truncated ORFs were up-regulated. Interestingly, two of these four genes demonstrating mycorrhiza-specific AS are related to the process of splicing, thus forming parts of the feedback loops involved in fine-tuning of gene expression during mycorrhization.

scholarly journals A Novel Nuclear Trafficking Module Regulates the Nucleocytoplasmic Localization of the Rabies Virus Interferon Antagonist, P Protein

2012 ◽  
Vol 287 (33) ◽  
pp. 28112-28121 ◽  
Author(s):  
Sibil Oksayan ◽  
Linda Wiltzer ◽  
Caitlin L. Rowe ◽  
Danielle Blondel ◽  
David A. Jans ◽  
...  
Keyword(s):  
Rabies Virus ◽  
Nuclear Trafficking ◽  
P Protein

scholarly journals Structural and Functional Characterization of the Phosphoprotein Central Domain of Spring Viremia of Carp Virus

2020 ◽  
Vol 94 (15) ◽  
Author(s):  
Zhao-Xi Wang ◽  
Shu-Bo Liu ◽  
Hongxin Guan ◽  
Long-Feng Lu ◽  
Jia-Gang Tu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Functional Characterization ◽  
Oligomeric State ◽  
Hydrophobic Surfaces ◽  
Central Domain ◽  
P Protein ◽  
Homologous Virus ◽  
Β Sheets ◽  
P Proteins

ABSTRACT Spring viremia of carp virus (SVCV) is a highly pathogenic Vesiculovirus in the common carp. The phosphoprotein (P protein) of SVCV is a multifunctional protein that acts as a polymerase cofactor and an antagonist of cellular interferon (IFN) response. Here, we report the 1.5-Å-resolution crystal structure of the P protein central domain (PCD) of SVCV (SVCVPCD). The PCD monomer consists of two β sheets, an α helix, and another two β sheets. Two PCD monomers pack together through their hydrophobic surfaces to form a dimer. The mutations of residues on the hydrophobic surfaces of PCD disrupt the dimer formation to different degrees and affect the expression of host IFN consistently. Therefore, the oligomeric state formation of the P protein of SVCV is an important mechanism to negatively regulate host IFN response. IMPORTANCE SVCV can cause spring viremia of carp with up to 90% lethality, and it is the homologous virus of the notorious vesicular stomatitis virus (VSV). There are currently no drugs that effectively cure this disease. P proteins of negative-strand RNA viruses (NSVs) play an essential role in many steps during the replication cycle and an additional role in immunosuppression as a cofactor. All P proteins of NSVs are oligomeric, but the studies on the role of this oligomerization mainly focus on the process of virus transcription or replication, and there are few studies on the role of PCD in immunosuppression. Here, we present the crystal structure of SVCVPCD. A new mechanism of immune evasion is clarified by exploring the relationship between SVCVPCD and host IFN response from a structural biology point of view. These findings may provide more accurate target sites for drug design against SVCV and provide new insights into the function of NSVPCD.

Dynamic transitions in the translocated phloem filament protein

2000 ◽  
Vol 27 (9) ◽  
pp. 733 ◽  
Author(s):  
Kirsten Leineweber ◽  
Alexander Schulz ◽  
Gary A. Thompson
Keyword(s):  
Disulfide Bonds ◽  
Assimilate Transport ◽  
Phloem Sap ◽  
Folding Intermediates ◽  
P Protein ◽  
Molecular Masses ◽  
P Proteins ◽  
The Stability ◽  
Filament Protein ◽  
Higher Sensitivity

This paper originates from a presentation at the International Conference on Assimilate Transport and Partitioning, Newcastle, NSW, August 1999 Recent evidence suggests that the P-proteins of Cucurbita maxima exist in at least two structural states: large polymers that are immobilized in individual sieve elements and small polymers or individual subunits that are translocated over long distances. We investigated variation in the structure of the phloem filament protein (phloem protein 1 or PP1) to determine the translocated form of the protein and its relationship to the polymerized state. It was demonstrated that the stability, folding state and assembly of the phloem filament protein rely on distinct intramolecular disulfide bonds. Acid trapping experiments combined with intergeneric grafts revealed that the phloem filament protein is translocated as an 88 kDa globular protein. By altering the pH of the collection buffer (pH 2–10), four individual conformational isoforms of PP1 with molecular masses of 81, 83, 85 and 88 kDa were consistently observed. The 81 kDa isoform represents the totally reduced phloem filament protein, the 83 and 85 kDa isoforms folding intermediates, and the 88 kDa its native soluble translocated form. The 83 and 85 kDa folding intermediates are susceptible to aggregation causing the gelation and formation of P-protein filaments in oxidized phloem sap. In contrast to the 88 kDa globular transport form, the 81, 83 and 85 kDa isoforms possibly exhibit lower stability, and therefore a higher sensitivity to proteolytic digestion.

Analysis of airway fluid protein concentration in neurogenic pulmonary edema

1987 ◽  
Vol 62 (2) ◽  
pp. 470-476 ◽  
Author(s):  
M. B. Maron
Keyword(s):  
Pulmonary Edema ◽  
Protein Concentration ◽  
Protein A ◽  
Volume Overload ◽  
Protein Fractions ◽  
Neurogenic Pulmonary Edema ◽  
P Protein ◽  
P Concentration ◽  
Endogenous Protein ◽  
Alpha Chloralose

Intracisternal administration of veratrine (40 micrograms/kg) in the alpha-chloralose-anesthetized dog produces fulminant neurogenic pulmonary edema (NPE). To determine whether the edema resulted from increased microvascular pressure or from increased permeability, the airway fluid-to-plasma protein (A/P) concentration ratios were compared for both total proteins and endogenous protein fractions of known molecular radii (37–114 A) from dogs with edema produced by either veratrine, alloxan (permeability edema), or combined left atrial pressure and volume overload (hemodynamic edema). High A/P ratios (0.98 +/- 0.05) were observed after alloxan administration, whereas lower values (0.54 +/- 0.04) were observed in hemodynamic edema. A/P ratios were observed after veratrine administration that formed a continuum (0.48–0.84) between these extremes. Veratrine animals with high overall A/P ratios exhibited elevated A/P ratios for all protein fractions, whereas animals with lower overall A/P ratios exhibited A/P protein fraction ratios similar to those observed in the hemodynamic group. These data indicate that both hemodynamic and increased permeability mechanisms may play a role to varying degrees in the development of this form of NPE.

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