scholarly journals Early Transcriptional Response of Human Neutrophils to Anaplasma phagocytophilum Infection

2005 ◽  
Vol 73 (12) ◽  
pp. 8089-8099 ◽  
Author(s):  
Bindu Sukumaran ◽  
Jason A. Carlyon ◽  
Ji-Lian Cai ◽  
Nancy Berliner ◽  
Erol Fikrig
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Anaplasma Phagocytophilum ◽  
Transcriptional Response ◽  
Human Neutrophils ◽  
Down Regulation ◽  
Granulocytic Ehrlichiosis ◽  
Reverse Transcription Pcr ◽  
Cell Gene Expression ◽  
Obligate Intracellular Pathogen

ABSTRACT Anaplasma phagocytophilum, an unusual obligate intracellular pathogen that persists within neutrophils, causes human anaplasmosis (previously known as human granulocytic ehrlichiosis). To study the effects of this pathogen on the transcriptional profile of its host cell, we performed a comprehensive DNA microarray analysis of the early (4-h) transcriptional response of human neutrophils to A. phagocytophilum infection. A. phagocytophilum infection resulted in the up- and down-regulation of 177 and 67 neutrophil genes, respectively. These data were verified by quantitative reverse transcription-PCR of selected genes. Notably, the up-regulation of many antiapoptotic genes, including the BCL2A1, BIRC3, and CFLAR genes, and the down-regulation of the proapoptotic TNFSF10 gene were observed. Genes involved in inflammation, innate immunity, cytoskeletal remodeling, and vesicular transport also exhibited differential expression. Vascular endothelial growth factor was also induced. These data suggest that A. phagocytophilum may alter selected host pathways in order to facilitate its survival within human neutrophils. To gain further insight into the bacterium's influence on host cell gene expression, this report presents a detailed comparative analysis of our data and other gene expression profiling studies of A. phagocytophilum-infected neutrophils and promyelocytic cell lines.

scholarly journals Silencing of Host Cell CYBB Gene Expression by the Nuclear Effector AnkA of the Intracellular Pathogen Anaplasma phagocytophilum

2009 ◽  
Vol 77 (6) ◽  
pp. 2385-2391 ◽  
Author(s):  
Jose C. Garcia-Garcia ◽  
Kristen E. Rennoll-Bankert ◽  
Shaaretha Pelly ◽  
Aaron M. Milstone ◽  
J. Stephen Dumler
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Anaplasma Phagocytophilum ◽  
Host Cells ◽  
Bacterial Survival ◽  
Defense Genes ◽  
Regulatory Regions ◽  
Transcriptional Regulatory ◽  
Cell Gene Expression ◽  
Host Chromatin

ABSTRACT Coevolution of intracellular bacterial pathogens and their host cells resulted in the appearance of effector molecules that when translocated into the host cell modulate its function, facilitating bacterial survival within the hostile host environment. Some of these effectors interact with host chromatin and other nuclear components. In this report, we show that the AnkA protein of Anaplasma phagocytophilum, which is translocated into the host cell nucleus, interacts with gene regulatory regions of host chromatin and is involved in downregulating expression of CYBB (gp91 phox ) and other key host defense genes. AnkA effector protein rapidly accumulated in nuclei of infected cells coincident with changes in CYBB transcription. AnkA interacted with transcriptional regulatory regions of the CYBB locus at sites where transcriptional regulators bind. AnkA binding to DNA occurred at regions with high AT contents. Mutation of AT stretches at these sites abrogated AnkA binding. Histone H3 acetylation decreased dramatically at the CYBB locus during A. phagocytophilum infection, particularly around AnkA binding sites. Transcription of CYBB and other defense genes was significantly decreased in AnkA-transfected HL-60 cells. These data suggest a mechanism by which intracellular pathogens directly regulate host cell gene expression mediated by nuclear effectors and changes in host chromatin structure.

scholarly journals Impact of Human Cytomegalovirus Latent Infection on Myeloid Progenitor Cell Gene Expression

2004 ◽  
Vol 78 (8) ◽  
pp. 4054-4062 ◽  
Author(s):  
Barry Slobedman ◽  
J. Lewis Stern ◽  
Anthony L. Cunningham ◽  
Allison Abendroth ◽  
Davide A. Abate ◽  
...  
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Human Cytomegalovirus ◽  
Latent Infection ◽  
Global Changes ◽  
Reverse Transcription Pcr ◽  
Myeloid Progenitor ◽  
Cell Gene Expression ◽  
Cell Gene ◽  
Host Genes

ABSTRACT Herpesviruses establish lifelong latent infections in their hosts. Human cytomegalovirus (CMV) targets a population of bone marrow-derived myeloid lineage progenitor cells that serve as a reservoir for reactivation; however, the mechanisms by which latent CMV infection is maintained are unknown. To gain insights into mechanisms of maintenance and reactivation, we employed microarrays of ∼26,900 sequence-verified human cDNAs to assess global changes in cellular gene expression during experimental CMV latent infection of granulocyte-macrophage progenitors (GM-Ps). This analysis revealed at least 29 host cell genes whose expression was increased and six whose expression was decreased during CMV latency. These changes in transcript levels appeared to be authentic, judging on the basis of further analysis of a subset by semiquantitative reverse transcription-PCR. This study provides a comprehensive snapshot of changes in host cell gene expression that result from latent infection and suggest that CMV regulates genes that encode proteins involved in immunity and host defense, cell growth, signaling, and transcriptional regulation. The host genes whose expression we found altered are likely to contribute to an environment that sustains latent infection.

scholarly journals Host Cell Gene Expression during Human Immunodeficiency Virus Type 1 Latency and Reactivation and Effects of Targeting Genes That Are Differentially Expressed in Viral Latency

2004 ◽  
Vol 78 (17) ◽  
pp. 9458-9473 ◽  
Author(s):  
Vyjayanthi Krishnan ◽  
Steven L. Zeichner
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Cell Lines ◽  
Lytic Replication ◽  
Replication Cycle ◽  
Differentially Expressed ◽  
Cellular Genes ◽  
Latently Infected ◽  
Cell Gene Expression ◽  
Infected Cells

ABSTRACT The existence of reservoirs of cells latently infected with human immunodeficiency virus (HIV) is a major obstacle to the elimination of HIV infection. We studied the changes in cellular gene expression that accompany the reactivation and completion of the lytic viral cycle in cell lines chronically infected with HIV-1. We found that several genes exhibited altered expression in the chronically infected cells compared to the uninfected parental cells prior to induction into lytic replication. A number of gene classes showed increased expression in the chronically infected cells, notably including genes encoding proteasomes, histone deacetylases, and many transcription factors. Following induction of the lytic replication cycle, we observed ordered, time-dependent changes in the cellular gene expression pattern. Approximately 1,740 genes, many of which fall into 385 known pathways, were differentially expressed (P < 0.001), indicating that completion of the HIV replication cycle is associated with distinct, temporally ordered changes in host cell gene expression. Maximum changes were observed in the early and intermediate phases of the lytic replication cycle. Since the changes in gene expression in chronically infected cells suggested that cells latently infected with HIV have a different gene expression profile than corresponding uninfected cells, we studied the expression profiles of three different chronically infected cell lines to determine whether they showed similar changes in common cellular genes and pathways. Thirty-two genes showed significant differential expression in all cell lines studied compared to their uninfected parental cell lines. Notable among them were cdc42 and lyn, which were downregulated and are required for HIV Nef binding and viral replication. Other genes previously unrelated to HIV latency or pathogenesis were also differentially expressed. To determine the effects of targeting products of the genes that were differentially expressed in latently infected cells, we treated the latently infected cells with a proteasome inhibitor, clastolactacystin-beta-lactone (CLBL), and an Egr1 activator, resveratrol. We found that treatment with CLBL and resveratrol stimulated lytic viral replication, suggesting that treatment of cells with agents that target cellular genes differentially expressed in latently infected cells can stimulate lytic replication. These findings may offer new insights into the interaction of the latently infected host cell and HIV and suggest therapeutic approaches for inhibiting HIV infection and for manipulating cells latently infected with HIV so as to trigger lytic replication.

scholarly journals Modulation of activation‐associated host cell gene expression by the apicomplexan parasite T heileria annulata

2012 ◽  
Vol 14 (9) ◽  
pp. 1434-1454 ◽  
Author(s):  
Zeeshan Durrani ◽  
William Weir ◽  
Sreerekha Pillai ◽  
Jane Kinnaird ◽  
Brian Shiels
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Apicomplexan Parasite ◽  
Cell Gene Expression ◽  
Cell Gene

scholarly journals A Bovine Lymphosarcoma Cell Line Infected with Theileria annulata Exhibits an Irreversible Reconfiguration of Host Cell Gene Expression

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e66833 ◽  
Author(s):  
Jane H. Kinnaird ◽  
William Weir ◽  
Zeeshan Durrani ◽  
Sreerekha S. Pillai ◽  
Margaret Baird ◽  
...  
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Cell Line ◽  
Theileria Annulata ◽  
Cell Gene Expression ◽  
Cell Gene

scholarly journals Semliki Forest Virus Nonstructural Protein 2 Is Involved in Suppression of the Type I Interferon Response

2007 ◽  
Vol 81 (16) ◽  
pp. 8677-8684 ◽  
Author(s):  
Lucy Breakwell ◽  
Pia Dosenovic ◽  
Gunilla B. Karlsson Hedestam ◽  
Mauro D'Amato ◽  
Peter Liljeström ◽  
...  
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Semliki Forest Virus ◽  
Nonstructural Protein ◽  
Nuclear Localization Sequence ◽  
Type I ◽  
Viral Mutant ◽  
Cell Gene Expression ◽  
Infected Cells ◽  
Cell Gene

ABSTRACT The type I interferons (IFNs) are potent mediators of antiviral immunity, and many viruses have developed means to block their expression or their effects. Semliki Forest virus (SFV) infection induces rapid and profound silencing of host cell gene expression, a process believed to be important for the inhibition of the IFN response. In SFV-infected cells, a large proportion of the nonstructural protein nsp2 is found in the nucleus, but a role for this localization has not been described. In this work we demonstrate that a viral mutant, SFV4-RDR, in which the nuclear localization sequence of nsp2 has been rendered inactive, induces a significantly more robust IFN response in infected cells. This mutant virus replicates at a rate similar to that of the parental SFV4 strain and also shuts off host cell gene expression to similar levels, indicating that the general cellular shutoff is not responsible for the inhibition of IFN expression. Further, the rate of virus-induced nuclear translocation of early IFN transcription factors was not found to differ between the wild-type and mutant viruses, indicating that the effect of nsp2 is at a later stage. These results provide novel information about the mode of action of this viral IFN antagonist.

scholarly journals Characterization of a Toxoplasma effector uncovers an alternative GSK3/β-catenin-regulatory pathway of inflammation

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Huan He ◽  
Marie-Pierre Brenier-Pinchart ◽  
Laurence Braun ◽  
Alexandra Kraut ◽  
Bastien Touquet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Regulatory Elements ◽  
Dense Granule ◽  
Effector Proteins ◽  
Immune Gene ◽  
Downstream Effects ◽  
Evolutionarily Conserved ◽  
Cell Gene Expression ◽  
Timely Fashion

The intracellular parasite Toxoplasma gondii, hijacks evolutionarily conserved host processes by delivering effector proteins into the host cell that shift gene expression in a timely fashion. We identified a parasite dense granule protein as GRA18 that once released in the host cell cytoplasm forms versatile complexes with regulatory elements of the β-catenin destruction complex. By interacting with GSK3/PP2A-B56, GRA18 drives β-catenin up-regulation and the downstream effects on host cell gene expression. In the context of macrophages infection, GRA18 induces the expression of a specific set of genes commonly associated with an anti-inflammatory response that includes those encoding chemokines CCL17 and CCL22. Overall, this study adds another original strategy by which T. gondii tachyzoites reshuffle the host cell interactome through a GSK3/β-catenin axis to selectively reprogram immune gene expression.

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