scholarly journals 143. Regulated, High Capacity Adenoviral Vectors Mediated Long-Term Gene Expression in the Brain Even in the Presence of a Peripheral Immune Response to Adenovirus

2005 ◽  
Vol 11 ◽  
pp. S58
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
High Capacity ◽  
Adenoviral Vectors ◽  
Peripheral Immune Response ◽  
The Brain

Abstract 312: Transcriptional and Posttranscriptional Circuitry in the Brain After Transient and Permanent Ischemia

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Fatiha Tabet ◽  
Sandy Lee ◽  
Luisa F Cuesta Torres ◽  
Michael G Levin ◽  
Grant R Drummond ◽  
...  
Keyword(s):  
Gene Expression ◽  
Validation Studies ◽  
Regulatory Networks ◽  
Functional Roles ◽  
Sham Procedure ◽  
Gene Regulatory ◽  
Neurological Processes ◽  
The Brain

Background: Stroke is a major neurovascular disease and a leading cause of mortality and long-term disability. Within cells of the brain, short non-encoding microRNAs (miRNAs) serve to modulate gene expression and likely contribute to most, neurological processes. However, miRNA changes in the brain tissue in response to stroke have not been reported. Aim: To investigate the functional roles of brain miRNAs and gene regulatory networks in stroke injury. Methods: Adult (8-12 weeks old) male C57Bl/6 mice underwent intraluminal filament-induced middle cerebral artery (MCA) occlusion. Permanent ischemia (ischemia no reperfusion, InoR; n=8) was achieved by occlusion for 24 h, and ischemia with reperfusion (IR; n=8) was completed after 30 min of MCA followed by 23.5 h of reperfusion. Sham-operated mice (n=8) were used as controls. Total RNA was isolated from mouse brains and gene arrays (Affymetrix) and miRNA arrays (TaqMan OpenArray microRNA) were performed. Validation studies were performed using RT-PCR and TaqMan Individual Assays. Results: Relative to the sham-operated mice, InoR significantly altered (p≤0.05; fold-change≥1.5) the levels of 471 genes (mRNA) in the brain. By contrast, IR resulted in only 114 significant changes in gene expression after 24 h. Brain miRNAs were also very sensitive to both ischemia and reperfusion. 28 miRNAs (11 down, 17 up) were significantly altered by InoR compared to the sham procedure. Likewise, 12 miRNAs (3 down, 9 up) were significantly altered with reperfusion compared to the sham procedure. Interestingly, we found 10 miRNAs to be significantly altered (5 up, 5 down) with ischemia (InoR/Sham), but were also significantly corrected towards normal Sham levels by 23.5 h reperfusion (IR/InoR). Validation studies confirmed that levels of multiple miRNAs were significantly altered with InoR. Reperfusion increased the levels of all these miRNAs. 48% (327/680) of the mRNAs that were altered were predicted targets of significantly altered miRNAs, and our results showed inverse directional changes. Conclusion: Results from our study show the role of miRNAs and post-transcriptional circuits in both adaptive and maladaptive responses to ischemic stroke and reperfusion.

Abstract WP564: Deep Immune Profiling of the Post-Stroke Peripheral Immune Response Reveals Tri-phasic Response and Correlations With Long-Term Cognitive Outcomes

Stroke ◽  
2019 ◽  
Vol 50 (Suppl_1) ◽  
Author(s):  
Amy S Tsai ◽  
Ketura Berry ◽  
Maxime M Beneyto ◽  
Dyani Gaudilliere ◽  
Edward A Ganio ◽  
...  
Keyword(s):  
Immune Response ◽  
Cognitive Outcomes ◽  
Phasic Response ◽  
Post Stroke ◽  
Peripheral Immune Response ◽  
Immune Profiling

scholarly journals Variation in the immune response to adenoviral vectors in the brain: influence of mouse strain, environmental conditions and priming

Gene Therapy ◽  
1999 ◽  
Vol 6 (4) ◽  
pp. 471-481 ◽  
Author(s):  
Y Ohmoto ◽  
M J A Wood ◽  
H M Charlton ◽  
K Kajiwara ◽  
V H Perry ◽  
...  
Keyword(s):  
Immune Response ◽  
Mouse Strain ◽  
Environmental Conditions ◽  
Adenoviral Vectors ◽  
The Brain

scholarly journals Regulatable Gutless Adenovirus Vectors Sustain Inducible Transgene Expression in the Brain in the Presence of an Immune Response against Adenoviruses

2006 ◽  
Vol 80 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Weidong Xiong ◽  
Shyam Goverdhana ◽  
Sandra A. Sciascia ◽  
Marianela Candolfi ◽  
Jeffrey M. Zirger ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Immune Response ◽  
Transgene Expression ◽  
High Capacity ◽  
Regulatory Elements ◽  
Murine Cytomegalovirus ◽  
Serious Adverse Events ◽  
Expression Levels ◽  
The Brain

ABSTRACT In view of recent serious adverse events and advances in gene therapy technologies, the use of regulatable expression systems is becoming recognized as indispensable adjuncts to successful clinical gene therapy. In the present work we optimized high-capacity adenoviral (HC-Ad) vectors encoding the novel tetracycline-dependent (TetOn)-regulatory elements for efficient and regulatable gene expression in the rat brain in vivo. We constructed two HC-Ad vectors encoding β-galactosidase (β-gal) driven by a TetOn system containing the rtTASsM2 transactivator and the tTSKid repressor under the control of the murine cytomegalovirus (mCMV) (HC-Ad-mTetON-β-Gal) or the human CMV (hCMV) promoter (HC-Ad-hTetON-β-Gal). Expression was tightly regulatable by doxycycline (Dox), reaching maximum expression in vivo at 6 days and returning to basal levels at 10 days following the addition or removal of Dox, respectively. Both vectors achieved higher transgene expression levels compared to the expression from vectors encoding the constitutive mCMV or hCMV promoter. HC-Ad-mTetON-β-Gal yielded the highest transgene expression levels and expressed in both neurons and astrocytes. Antivector immune responses continue to limit the clinical use of vectors. We thus tested the inducibility and longevity of HC-Ad-mediated transgene expression in the brain of rats immunized against adenovirus by prior intradermal injections of RAds. Regulated transgene expression from HC-Ad-mTetON-β-Gal remained active even in the presence of a significant systemic immune response. Therefore, these vectors display two coveted characteristics of clinically useful vectors, namely their regulation and effectiveness even in the presence of prior immunization against adenovirus.

scholarly journals Differential Methylation of Epstein-Barr Virus Latency Promoters Facilitates Viral Persistence in Healthy Seropositive Individuals

1999 ◽  
Vol 73 (12) ◽  
pp. 9959-9968 ◽  
Author(s):  
Emily J. Paulson ◽  
Samuel H. Speck
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Viral Genome ◽  
Epstein Barr Virus ◽  
Critical Role ◽  
Viral Gene ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) establishes a life-long infection in humans, with distinct viral latency programs predominating during acute and chronic phases of infection. Only a subset of the EBV latency-associated antigens present during the acute phase of EBV infection are expressed in the latently infected memory B cells that serve as the long-term EBV reservoir. Since the EBV immortalization program elicits a potent cellular immune response, downregulation of viral gene expression in the long-term latency reservoir is likely to facilitate evasion of the immune response and persistence of EBV in the immunocompetent host. Tissue culture and tumor models of restricted EBV latency have consistently demonstrated a critical role for methylation of the viral genome in maintaining the restricted pattern of latency-associated gene expression. Here we extend these observations to demonstrate that the EBV genomes in the memory B-cell reservoir are also heavily and discretely methylated. This analysis reveals that methylation of the viral genome is a normal aspect of EBV infection in healthy immunocompetent individuals and is not restricted to the development of EBV-associated tumors. In addition, the pattern of methylation very likely accounts for the observed inhibition of the EBV immortalization program and the establishment and maintenance of a restricted latency program. Thus, EBV appears to be the first example of a parasite that usurps the host cell-directed methylation system to regulate pathogen gene expression and thereby establish a chronic infection.

Cellular and molecular neuroscience of alcoholism

1997 ◽  
Vol 77 (1) ◽  
pp. 1-20 ◽  
Author(s):  
I. Diamond ◽  
A. S. Gordon
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Molecular Level ◽  
Cellular Functions ◽  
Short Term ◽  
Medical Disorders ◽  
Molecular Neuroscience ◽  
Long Term Changes ◽  
The Brain

Recent advances in neuroscience have made it possible to investigate the pathophysiology of alcoholism at a cellular and molecular level. Evidence indicates that ethanol affects hormone- and neurotransmitter-activated signal transduction, leading to short-term changes in regulation of cellular functions and long-term changes in gene expression. Such changes in the brain probably underlie many of the acute and chronic neurological events in alcoholism. In addition, genetic vulnerability also plays a role in alcoholism and, perhaps, in alcoholic medical disorders.

scholarly journals Memory immune response: a major challenge in vaccination

2012 ◽  
Vol 3 (5) ◽  
pp. 479-486 ◽  
Author(s):  
Antonella Prisco ◽  
Piergiuseppe De Berardinis
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Vaccine Development ◽  
Immune Memory ◽  
Gene Expression Signatures ◽  
Antibody Titers ◽  
Memory Immune Response ◽  
Protective Threshold

AbstractA crucial challenge for vaccine development is to design vaccines that induce a long-lasting protective immune response, i.e., immune memory. The persistence of antigen-specific antibody titers over a protective threshold, and the ability to exibit a ‘recall response’ to a subsequent encounter with an antigen have long been the only measurable correlates of vaccine take and immune memory development, suffering from the disadvantage of relying on long-term monitoring of the immune response. In the last few years, advances in the technologies for the identification and characterization of the cell subsets and molecular pathways involved in the immune response to vaccination have allowed innovative approaches to the identification of early correlates of immune memory. In this review, we discuss recent data and hypotheses on early correlates of the development of immune memory, with special emphasis on the gene expression signatures that underlie the self-renewal ability of some lymphocyte subsets, and their similarities with gene expression signatures in stem cells.

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