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 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 Distinct single cell gene expression in peripheral blood monocytes correlates with tumor necrosis factor inhibitor treatment response groups defined by type I interferon in rheumatoid arthritis

2019 ◽  
Author(s):  
Theresa L. Wampler Muskardin ◽  
Wei Fan ◽  
Zhongbo Jin ◽  
Mark A. Jensen ◽  
Jessica M. Dorschner ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Type I ◽  
Cell Gene Expression ◽  
Response Group ◽  
Cell Gene ◽  
Α Activity ◽  
Necrosis Factor

AbstractPreviously, we demonstrated that type I IFN (IFNβ/α) activity can predict non-response to tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). In this study, we examine the biology of TNFi non-response in monocytes from RA patients. We compared single cell gene expression in purified classical (CL, n=342) and non-classical (NC, n=359) monocytes. RA patients were grouped according to their pre-TNFi IFNβ/α activity: those likely to have EULAR no response (non-response group, IFNβ/α 0 or >1.3, n=9) and those likely to have EULAR moderate or good response (response group, IFNβ/α > 0 and ≤1.3, n=6). Major differences in gene expression were apparent in principal component and unsupervised cluster analyses. CL monocytes from the non-response group were unlikely to express JAK1 and IFI27 (p <0.0001 and p 0.0005, respectively). In NC monocytes from the same group, expression of IFNAR1, IRF1, TNFA, TLR4 (p ≤0.0001 for each) and others was enriched. Interestingly, JAK1 expression was absent in CL and NC monocytes from 9 patients. This pattern strongly associated with the non-response IFNβ/α group, suggesting a major biological difference between JAK1 expressors and non-expressors. The type I IFN activity that was previously found to predict TNFi response associated with changes in gene expression in monocytes that suggest differential IFN pathway activation in RA patients who are either likely to respond or to have no response to TNFi. This work could suggest mechanisms for TNFi non-response, and potential therapeutic strategies for those patients unlikely to respond to TNFi.

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 Global Suppression of the Host Antiviral Response by Ebola- and Marburgviruses: Increased Antagonism of the Type I Interferon Response Is Associated with Enhanced Virulence

2006 ◽  
Vol 80 (6) ◽  
pp. 3009-3020 ◽  
Author(s):  
John C. Kash ◽  
Elke Mühlberger ◽  
Victoria Carter ◽  
Melanie Grosch ◽  
Olivia Perwitasari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Phase Proteins ◽  
Transcriptional Profiling ◽  
Regulation Of Gene Expression ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifn ◽  
Cell Gene Expression ◽  
Infected Cells ◽  
Immune Related Genes

ABSTRACT We studied the effect of filovirus infection on host cell gene expression by characterizing the regulation of gene expression responses in human liver cells infected with Zaire Ebolavirus (ZEBOV), Reston Ebolavirus (REBOV), and Marburgvirus (MARV), using transcriptional profiling and bioinformatics. Expression microarray analysis demonstrated that filovirus infection resulted in the up-regulation of immune-related genes and the down-regulation of many coagulation and acute-phase proteins. These studies further revealed that a common feature of filovirus virulence is suppression of key cellular antiviral responses, including TLR-, interferon (IFN) regulatory factor 3-, and PKR-related pathways. We further showed that ZEBOV and MARV were more potent antagonists of the IFN response and inhibited the expression of most of the IFN-stimulated genes (ISGs) observed in mock-infected IFN-α-2b treated cells, compared to REBOV infection, which activated more than 20% of these ISGs. Finally, we examined IFN-related gene expression in filovirus-infected cells treated with IFN-α-2b. These experiments revealed that a majority of genes induced in mock-infected cells treated with type I IFN were antagonized in treated ZEBOV- and MARV-infected cells, while in contrast, REBOV infection resulted in a significant increase in ISG expression. Analysis of STAT1 and -2 phosphorylation following IFN treatment showed a significant reduction of STAT phosphorylation for MARV but not for ZEBOV and REBOV, indicating that different mechanisms might be involved in antagonizing IFN signaling pathways by the different filovirus species. Taken together, these studies showed a correlation between antagonism of type I IFN responses and filovirus virulence.

Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment

2003 ◽  
Vol 307 (4) ◽  
pp. 1029-1037 ◽  
Author(s):  
Sylvia Lee-Huang ◽  
Li Zhang ◽  
Philip Lin Huang ◽  
Young-Tae Chang ◽  
Paul L Huang
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Leaf Extract ◽  
Olive Leaf ◽  
Olive Leaf Extract ◽  
Cell Gene Expression ◽  
Cell Gene ◽  
Anti Hiv ◽  
Hiv 1

Impact of the interaction between adenovirus E1A and CtBP on host cell gene expression

2005 ◽  
Vol 113 (1) ◽  
pp. 51-63 ◽  
Author(s):  
Cecilia Johansson ◽  
Hongxing Zhao ◽  
Edyta Bajak ◽  
Fredrik Granberg ◽  
Ulf Pettersson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Adenovirus E1a ◽  
Cell Gene Expression ◽  
Cell Gene
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