scholarly journals Faculty Opinions recommendation of Genome replication dynamics of a bacteriophage and its satellite reveal strategies for parasitism and viral restriction.

2021 ◽  
Author(s):  
Jan Roelof van der Meer ◽  
Nicolas Carraro
Keyword(s):  
Genome Replication ◽  
Viral Restriction

scholarly journals Genome replication dynamics of a bacteriophage and its satellite reveal strategies for parasitism and viral restriction

2019 ◽  
Author(s):  
Zachary K Barth ◽  
Tania V Silvas ◽  
Angus Angermeyer ◽  
Kimberley D Seed
Keyword(s):  
Dna Replication ◽  
Vibrio Cholerae ◽  
Host Cells ◽  
Initiation Factor ◽  
Cell Populations ◽  
Lytic Phage ◽  
Genome Replication ◽  
Origin Of Replication ◽  
New Host ◽  
Viral Restriction

Abstract Phage-inducible chromosomal island-like elements (PLEs) are bacteriophage satellites found in Vibrio cholerae. PLEs parasitize the lytic phage ICP1, excising from the bacterial chromosome, replicating, and mobilizing to new host cells following cell lysis. PLEs protect their host cell populations by completely restricting the production of ICP1 progeny. Previously, it was found that ICP1 replication was reduced during PLE(+) infection. Despite robust replication of the PLE genome, relatively few transducing units are produced. We investigated if PLE DNA replication itself is antagonistic to ICP1 replication. Here we identify key constituents of PLE replication and assess their role in interference of ICP1. PLE encodes a RepA_N initiation factor that is sufficient to drive replication from the PLE origin of replication during ICP1 infection. In contrast to previously characterized bacteriophage satellites, expression of the PLE initiation factor was not sufficient for PLE replication in the absence of phage. Replication of PLE was necessary for interference of ICP1 DNA replication, but replication of a minimalized PLE replicon was not sufficient for ICP1 DNA replication interference. Despite restoration of ICP1 DNA replication, non-replicating PLE remained broadly inhibitory against ICP1. These results suggest that PLE DNA replication is one of multiple mechanisms contributing to ICP1 restriction.

scholarly journals Genome replication dynamics of a bacteriophage and its satellite reveal strategies for parasitism and viral restriction

2019 ◽  
Author(s):  
Zachary K Barth ◽  
Tania V Silvas ◽  
Angus Angermeyer ◽  
Kimberley D Seed
Keyword(s):  
Dna Replication ◽  
Vibrio Cholerae ◽  
Host Cells ◽  
Initiation Factor ◽  
Cell Populations ◽  
Lytic Phage ◽  
Genome Replication ◽  
Origin Of Replication ◽  
New Host ◽  
Viral Restriction

ABSTRACTPhage-inducible chromosomal island-like elements (PLEs) are bacteriophage satellites found inVibrio cholerae. PLEs parasitize the lytic phage ICP1, excising from the bacterial chromosome, replicating, and mobilizing to new host cells following cell lysis. PLEs protect their host cell populations by completely restricting the production of ICP1 progeny. Previously, it was found that ICP1 replication was reduced during PLE(+) infection. Despite robustly replicating its genome, PLE produces relatively few transducing units, leading us to investigate if PLE DNA replication itself is antagonistic to ICP1 replication. Here we identify key constituents of PLE replication and assess their role in interference of ICP1. PLE encodes a RepA_N initiation factor that is sufficient to drive replication from the PLE origin of replication during ICP1 infection. In contrast to previously characterized bacteriophage satellites, expression of the PLE initiation factor was not sufficient for PLE replication in the absence of phage. Replication of PLE was necessary for interference of ICP1 DNA replication, but replication of a minimalized PLE replicon was not sufficient for ICP1 DNA replication interference. Despite restoration of ICP1 DNA replication, non-replicating PLE remained broadly inhibitory against ICP1. These results suggest that PLE DNA replication is one of multiple mechanisms contributing to ICP1 restriction.

scholarly journals The C-terminal domain of feline and bovine SAMHD1 proteins has a crucial role in lentiviral restriction

2020 ◽  
Vol 295 (13) ◽  
pp. 4252-4264 ◽  
Author(s):  
Chu Wang ◽  
Kaikai Zhang ◽  
Lina Meng ◽  
Xin Zhang ◽  
Yanan Song ◽  
...  
Keyword(s):  
Proteasomal Degradation ◽  
Acid Sites ◽  
Accessory Protein ◽  
Restriction Profile ◽  
Biological Functions ◽  
Terminal Domain ◽  
Functional Regions ◽  
Viral Restriction ◽  
Primate Lentiviruses

SAM and HD domain-containing protein 1 (SAMHD1) is a host factor that restricts reverse transcription of lentiviruses such as HIV in myeloid cells and resting T cells through its dNTP triphosphohydrolase (dNTPase) activity. Lentiviruses counteract this restriction by expressing the accessory protein Vpx or Vpr, which targets SAMHD1 for proteasomal degradation. SAMHD1 is conserved among mammals, and the feline and bovine SAMHD1 proteins (fSAM and bSAM) restrict lentiviruses by reducing cellular dNTP concentrations. However, the functional regions of fSAM and bSAM that are required for their biological functions are not well-characterized. Here, to establish alternative models to investigate SAMHD1 in vivo, we studied the restriction profile of fSAM and bSAM against different primate lentiviruses. We found that both fSAM and bSAM strongly restrict primate lentiviruses and that Vpx induces the proteasomal degradation of both fSAM and bSAM. Further investigation identified one and five amino acid sites in the C-terminal domain (CTD) of fSAM and bSAM, respectively, that are required for Vpx-mediated degradation. We also found that the CTD of bSAM is directly involved in mediating bSAM's antiviral activity by regulating dNTPase activity, whereas the CTD of fSAM is not. Our results suggest that the CTDs of fSAM and bSAM have important roles in their antiviral functions. These findings advance our understanding of the mechanism of fSAM- and bSAM-mediated viral restriction and might inform strategies for improving HIV animal models.

scholarly journals Small Antisense DNA-Based Gene Silencing Enables Cell-Free Bacteriophage Manipulation and Genome Replication

2021 ◽  
Author(s):  
Kilian Vogele ◽  
Elisabeth Falgenhauer ◽  
Sophie von Schönberg ◽  
Friedrich C. Simmel ◽  
Tobias Pirzer
Keyword(s):  
Gene Silencing ◽  
Genome Replication ◽  
Antisense Dna

scholarly journals SUMOylation of SAMHD1 at Lysine 595 is required for HIV-1 restriction in non-cycling cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Charlotte Martinat ◽  
Arthur Cormier ◽  
Joëlle Tobaly-Tapiero ◽  
Noé Palmic ◽  
Nicoletta Casartelli ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Reverse Transcription ◽  
Immune Cells ◽  
Viral Restriction ◽  
Antiviral Function ◽  
Hiv 1 ◽  
Constitutively Active

AbstractSAMHD1 is a cellular triphosphohydrolase (dNTPase) proposed to inhibit HIV-1 reverse transcription in non-cycling immune cells by limiting the supply of the dNTP substrates. Yet, phosphorylation of T592 downregulates SAMHD1 antiviral activity, but not its dNTPase function, implying that additional mechanisms contribute to viral restriction. Here, we show that SAMHD1 is SUMOylated on residue K595, a modification that relies on the presence of a proximal SUMO-interacting motif (SIM). Loss of K595 SUMOylation suppresses the restriction activity of SAMHD1, even in the context of the constitutively active phospho-ablative T592A mutant but has no impact on dNTP depletion. Conversely, the artificial fusion of SUMO2 to a non-SUMOylatable inactive SAMHD1 variant restores its antiviral function, a phenotype that is reversed by the phosphomimetic T592E mutation. Collectively, our observations clearly establish that lack of T592 phosphorylation cannot fully account for the restriction activity of SAMHD1. We find that SUMOylation of K595 is required to stimulate a dNTPase-independent antiviral activity in non-cycling immune cells, an effect that is antagonized by cyclin/CDK-dependent phosphorylation of T592 in cycling cells.

scholarly journals A slow, efficient and safe nanoplatform of tailored ZnS QD-mycophenolic acid conjugates for in vitro drug delivery against dengue virus 2 genome replication

2020 ◽  
Vol 2 (12) ◽  
pp. 5777-5789
Author(s):  
Ranjeet Dungdung ◽  
Manikanta Bayal ◽  
Lathika Valliyott ◽  
Unnikrishnan Unniyampurath ◽  
Swapna S. Nair ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Dengue Virus ◽  
Mycophenolic Acid ◽  
Genome Replication ◽  
Effective Delivery

The graphical abstract represents the synthesis of size engineered ZnS QDs for conjugating anti-viral drug (MPA) and its safe and effective delivery against cytoplasmically replicating dengue virus 2.

scholarly journals Snapshots of a Non-Canonical RdRP in Action

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1260
Author(s):  
Diego S. Ferrero ◽  
Michela Falqui ◽  
Nuria Verdaguer
Keyword(s):  
Metal Ion ◽  
Rna Viruses ◽  
Ion Binding ◽  
Genome Replication ◽  
Metal Ion Binding ◽  
Insect Virus ◽  
X Ray ◽  
Template Strand ◽  
Nucleotide Incorporation ◽  
Elongation Process

RNA viruses typically encode their own RNA-dependent RNA polymerase (RdRP) to ensure genome replication and transcription. The closed “right hand” architecture of RdRPs encircles seven conserved structural motifs (A to G) that regulate the polymerization activity. The four palm motifs, arranged in the sequential order A to D, are common to all known template dependent polynucleotide polymerases, with motifs A and C containing the catalytic aspartic acid residues. Exceptions to this design have been reported in members of the Permutotetraviridae and Birnaviridae families of positive single stranded (+ss) and double-stranded (ds) RNA viruses, respectively. In these enzymes, motif C is located upstream of motif A, displaying a permuted C–A–B–D connectivity. Here we study the details of the replication elongation process in the non-canonical RdRP of the Thosea asigna virus (TaV), an insect virus from the Permutatetraviridae family. We report the X-ray structures of three replicative complexes of the TaV polymerase obtained with an RNA template-primer in the absence and in the presence of incoming rNTPs. The structures captured different replication events and allowed to define the critical interactions involved in: (i) the positioning of the acceptor base of the template strand, (ii) the positioning of the 3’-OH group of the primer nucleotide during RNA replication and (iii) the recognition and positioning of the incoming nucleotide. Structural comparisons unveiled a closure of the active site on the RNA template-primer binding, before rNTP entry. This conformational rearrangement that also includes the repositioning of the motif A aspartate for the catalytic reaction to take place is maintained on rNTP and metal ion binding and after nucleotide incorporation, before translocation.

scholarly journals Developmental differences in genome replication program and origin activation

2020 ◽  
Vol 48 (22) ◽  
pp. 12751-12777
Author(s):  
Cathia Rausch ◽  
Patrick Weber ◽  
Paulina Prorok ◽  
David Hörl ◽  
Andreas Maiser ◽  
...  
Keyword(s):  
Dna Replication ◽  
Single Molecule ◽  
Embryonic Stem ◽  
S Phase ◽  
Developmental Differences ◽  
Centromeric Heterochromatin ◽  
Genome Replication ◽  
Origin Activation ◽  
Spatio Temporal ◽  
Mes Cells

Abstract To ensure error-free duplication of all (epi)genetic information once per cell cycle, DNA replication follows a cell type and developmental stage specific spatio-temporal program. Here, we analyze the spatio-temporal DNA replication progression in (un)differentiated mouse embryonic stem (mES) cells. Whereas telomeres replicate throughout S-phase, we observe mid S-phase replication of (peri)centromeric heterochromatin in mES cells, which switches to late S-phase replication upon differentiation. This replication timing reversal correlates with and depends on an increase in condensation and a decrease in acetylation of chromatin. We further find synchronous duplication of the Y chromosome, marking the end of S-phase, irrespectively of the pluripotency state. Using a combination of single-molecule and super-resolution microscopy, we measure molecular properties of the mES cell replicon, the number of replication foci active in parallel and their spatial clustering. We conclude that each replication nanofocus in mES cells corresponds to an individual replicon, with up to one quarter representing unidirectional forks. Furthermore, with molecular combing and genome-wide origin mapping analyses, we find that mES cells activate twice as many origins spaced at half the distance than somatic cells. Altogether, our results highlight fundamental developmental differences on progression of genome replication and origin activation in pluripotent cells.

scholarly journals Genome-Wide Analyses Reveal Genetic Convergence of Prolificacy between Goats and Sheep

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 480
Author(s):  
Lin Tao ◽  
Xiaoyun He ◽  
Yanting Jiang ◽  
Yufang Liu ◽  
Yina Ouyang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Litter Size ◽  
Luteal Phase ◽  
Antigen Processing ◽  
Osteoclast Differentiation ◽  
Follicular Phase ◽  
Comparative Genomic ◽  
Genome Replication ◽  
Viral Genome Replication ◽  
Transcriptomic Level

The litter size of domestic goats and sheep is an economically important trait that shows variation within breeds. Strenuous efforts have been made to understand the genetic mechanisms underlying prolificacy in goats and sheep. However, there has been a paucity of research on the genetic convergence of prolificacy between goats and sheep, which likely arose because of similar natural and artificial selection forces. Here, we performed comparative genomic and transcriptomic analyses to identify the genetic convergence of prolificacy between goats and sheep. By combining genomic and transcriptomic data for the first time, we identified this genetic convergence in (1) positively selected genes (CHST11 and SDCCAG8), (2) differentially expressed genes (SERPINA14, RSAD2, and PPIG at follicular phase, and IGF1, GPRIN3, LIPG, SLC7A11, and CHST15 at luteal phase), and (3) biological pathways (genomic level: osteoclast differentiation, ErbB signaling pathway, and relaxin signaling pathway; transcriptomic level: the regulation of viral genome replication at follicular phase, and protein kinase B signaling and antigen processing and presentation at luteal phase). These results indicated the potential physiological convergence and enhanced our understanding of the overlapping genetic makeup underlying litter size in goats and sheep.

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