Resume

• 1570810

  TIME Person of the Year

  (Shared award)\nhttp://content.time.com/time/magazine/article/0

  00.html

  TIME Magazine

  Outstanding Oral Presentation

  Behavior

  Biology and Chemistry Conference

  NIDA-IRP Mentoring Award for Fellows

  Nominated award recognizing my commitment to mentoring younger scientists\n\nMore details here: http://irp.nih.gov/catalyst/v21i4/four-generations-of-mentors-and-more\n

  National Institute on Drug Abuse

  Deans' Scholar

  University of Southern California

  Steinberg Fund Travel Award

  Competitive research award providing travel funds.

  Oregon Health & Science University Department of Physiology & Pharmacology

  Fellows’ Award for Research Excellence

  Competitive research award providing travel support funds

  National Institutes of Health

  Fellows’ Award for Research Excellence

  Competitive research award providing travel support funds

  National Institutes of Health

  Behavior

  Biology and Chemistry Conference Travel Award

  Competitive research travel award providing travel support funds and an oral presentation opportunity

  Behavior

  Biology and Chemistry Conference

  Assistant Professor Travel Grant

  Rowan University

  National Graduate Student Research Festival invitee

  Competitive application to present thesis research at NIH

  National Institutes of Health

• 2014

  Baltimore

  Maryland Area

  In vitro and in vivo pharmacological evaluation of novel pharmacotherapeutics for the treatment of drug addiction and other neuropsychiatric disorders:\n\n○ Evaluation of novel metabotropic glutamate receptor subtype 5 (mGlu5; mGluR5) negative allosteric modulators in vitro and in animal models of anxiety and cocaine addiction.\n > Keck TM

  Zou M-F

  Zhang P

  Rutledge RP

  Newman AH. (2012) Metabotropic glutamate receptor subtype 5 negative allosteric modulators as novel tools for in vivo investigation. ACS Med. Chem. Lett. 3(7): 544–549.\n > Keck TM

  Bi G-H

  Yang H-J

  Zhang H-Y

  Srivastava R

  Gardner EL

  Newman AH

  Xi Z-X. (2013) Fenobam sulfate inhibits cocaine-taking and cocaine-seeking behavior in rats: implications for translation. Psychopharmacology. 229(2): 253–265.\n > Keck TM

  Zou M-F

  Bi G-H

  Zhang H-Y

  Wang X-F

  Yang H-J

  Srivastava R

  Gardner EL

  Xi Z-X

  Newman AH. (2013) A novel mGluR5 antagonist

  MFZ 10-7

  inhibits cocaine-taking and cocaine-seeking behavior in rats. Addiction Biology. In press; E-pub September 4

  2013.\n\n○ Evaluation of novel dopamine D3 receptor-selective antagonists in vitro and in animal models of methamphetamine addiction.\n > Keck TM

  Burzynski C

  Shi L

  Newman AH. Beyond small molecule SAR – using the D3 receptor crystal structure to guide drug design. (2013) Invited review for Advances in Pharmacology. Volume 69

  Pages 267–300.\n\n○ Analyze the behavioral effects of methamphetamine neurotoxicity in animal models of cognition/memory with corresponding neurochemical and epigenetic marker evaluation.\n\n○ Determine the biased signaling properties of dopamine D2 receptor-selective agonists in vitro.

  IRTA Postdoctoral Fellow

  The National Institute on Drug Abuse (NIDA)

  Studied the influence of dopamine D4 receptor signaling on the behavioral responsiveness of mice to novel and anxiolytic stimuli and and the psychostimulant methylphenidate\n\n > Keck TM

  Suchland KL

  Jimenez CC

  Grandy DK. (2013) Dopamine D4 receptor deficiency in mice alters behavioral responses to anxiogenic stimuli and the psychostimulant methylphenidate. Pharmacology

  Biochemistry and Behavior. 103(4): 831–841.\n\nAdditional graduate research explored:\n\n○ Trace amine-associated receptor 1 (TAAR1) signaling in response to monoaminergic drugs\n\n○ Transcriptional effects of psychostimulant exposure in the mouse cortex via microarray\n\n○ Immune evasion by human cytomegalovirus\n\n > DeFilippis VR

  Robinson B

  Keck TM

  Hansen SG

  Nelson JA

  Früh KJ. (2006) Interferon regulatory factor 3 is necessary for induction of antiviral genes during human cytomegalovirus infection. J. Virol. 80(2): 1032–7.

  Ph.D. student

  Portland

  Oregon Area

  OHSU

  Vice President

  Mid-Atlantic Pharmacological Society

  Rowan University

  Society for Neuroscience-Greater Baltimore Chapter Poster Award

  Competitive award given to research presentations at annual meeting

  Society for Neuroscience-Greater Baltimore Chapter

  Behavior

  Biology and Chemistry Conference Travel Award

  Competitive research travel award providing travel support funds and an oral presentation opportunity

  Behavior

  Biology and Chemistry Conference

  NIH Postdoctoral Mentor Award

  Competitive award to mentor an outstanding community college student as part of the NIH's Summer Student Enrichment Program

  National Institutes of Health

  Deans' Scholar

  University of Southern California

  International Society of Neurochemistry Travel Award

  Competitive research award providing travel funds to present at annual society meeting

  International Society of Neurochemistry

  Maharaj Ticku Memorial Travel Fellowship for New Investigators Award

  The Maharaj Ticku Travel Fellowship is awarded annually to a new investigator who has completed but is not more than 4 years beyond completion of postdoctoral training and who has a full time position in academia and/or research. http://uthscsa.edu/artt/bbc/TravelAwards.asp

  Behavior

  Biology and Chemistry Conference

  Tartar Research Fellowship

  Competitive research award providing travel fund support

  Oregon Health & Science University

  Deans' Scholar

  University of Southern California

  Frances R. Lax Faculty Development Award

  Rowan University

• 2012

  ACS Med Chem Lett. 2012. 3(7):544-549\n\nNegative allosteric modulators (NAMs) of metabotropic glutamate receptor subtype 5 (mGluR5) have shown promising results in preclinical models for anxiety and drug abuse. Here we describe a series of aryl-substituted alkynyl analogues of the prototypic mGluR5 NAM 2-methyl-6-(phenylethynyl)pyridine (MPEP

  1). Displacement of [(3)H]1 binding in rat brain membranes showed that several of these novel compounds displayed high affinity binding (K(i) < 10 nM) for mGluR5

  with up to a 24-fold increase in affinity over 1. Replacements of the 2-position Me on the pyridyl ring of 1 along with various 3'-CN

  5'-substitutions were generally well tolerated. All of the active analogues in this series had cLogP values in the 2-5 range and displayed inverse agonist characteristics in an ELISA-based assay of G(q)α-mediated IP3 production. Compounds 7i and 7j produced in vivo effects in mouse models of anxiety-like behaviors more potently than 1 or 3-((2-methyl-1

  3-thiazol-4-yl)ethynyl)pyridine (MTEP

  2)

  supporting their utility as in vivo tools.\n\nACS Med. Chem. Lett.

  3 (7)

  pp 544–549\nhttp://pubs.acs.org/doi/abs/10.1021/ml3000726

  Metabotropic Glutamate Receptor Subtype 5 Negative Allosteric Modulators as Novel Tools for In Vivo Investigation

  Thomas

  UCLA

  OHSU

  The National Institute on Drug Abuse (NIDA)

  Rowan University

  Studied the regulation of oligodendrocyte development and myelination by two proteins: K+ channel Kv3.1 and the tight-junction protein OSP/claudin-11\n\n > Tiwari-Woodruff S

  Beltran-Parrazal L

  Charles A

  Keck T

  Vu T

  Bronstein J. (2006) K+ channel Kv3.1 associates with OSP/claudin-11 and regulates oligodendrocyte development and myelination. Am. J. Physiol. Cell. Physiol. 291(4): C687–98.

  Reseach associate

  Greater Los Angeles Area

  UCLA

  Greater Philadelphia Area

  Department of Chemistry & Biochemistry\nDepartment of Molecular & Cellular Biosciences\nCollege of Science and Mathematics\n\nPrimary courses taught:\nGeneral Aspects of Pharmacology\nBiochemistry\nMedical Biochemistry\n\nResearch mentor for >100 undergraduate and M.S. students thus far!\n\nResearch focus: in vitro & in vivo pharmacology and medications development for neuropsychiatric disorders. Current projects include drug discovery for schizophrenia

  pain

  Alzheimer's disease

  and drug addiction.

  Associate Professor

  Rowan University

• 2004

  Ph.D.

  Physiology & pharmacology

  Oregon Health and Science University

• 1999

  B.S.

  Biomedical-biochemical engineering

  University of Southern California

• 5

  Novel 1-

  5-

  and 8-substituted analogues of sumanirole (1)

  a dopamine D2/D3 receptor (D2R/D3R) agonist

  were synthesized. Binding affinities at both D2R and D3R were higher when determined in competition with the agonist radioligand [3H]7-hydroxy-N

  N-dipropyl-2-aminotetralin (7-OH-DPAT) than with the antagonist radioligand [3H]N-methylspiperone. Although 1 was confirmed as a D2R-preferential agonist

  its selectivity in binding and functional studies was lower than previously reported. All analogues were determined to be D2R/D3R agonists in both GoBRET and mitogenesis functional assays. Loss of efficacy was detected for the N-1-substituted analogues at D3R. In contrast

  the N-5-alkyl-substituted analogues

  and notably the n-butyl-arylamides (22b and 22c)

  all showed improved affinity at D2R over 1 with neither a loss of efficacy nor an increase in selectivity. Computational modeling provided a structural basis for the D2R selectivity of 1

  illustrating how subtle differences in the highly homologous orthosteric binding site (OBS) differentially affect D2R/D3R affinity and functional efficacy.

  Novel Analogues of (R)-5-(Methylamino)-5

  6-dihydro-4 H-imidazo [4

  1-ij] quinolin-2 (1 H)-one (Sumanirole) Provide Clues to Dopamine D2/D3 Receptor Agonist Selectivity

  Eliot L. Gardner

  Ratika Srivastava

  Hong-Ju Yang

  Hai-Ying Zhang

  Guo-Hua Bi

  Mu-Fa Zou

  Addict Biol. 2014. 19(2):195-209\n\nPre-clinical studies suggest that negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 5 (mGluR5)

  including 2-methyl-6-(phenylethynyl)pyridine (MPEP)

  3-[(2-methyl-1

  3-thiazol-4-yl)ethynyl]pyridine (MTEP) and fenobam are highly effective in attenuating drug-taking and drug-seeking behaviors. However

  both MPEP and MTEP have no translational potential for use in humans because of their off-target effects and short half-lives. Here

  we report that 3-fluoro-5-[(6-methylpyridin-2-yl)ethynyl]benzonitrile (MFZ 10-7)

  a novel mGluR5 NAM

  is more potent and selective than MPEP

  MTEP and fenobam in both in vitro binding and functional assays. Similar to MTEP

  intraperitoneal administration of MFZ 10-7 inhibited intravenous cocaine self-administration

  cocaine-induced reinstatement of drug-seeking behavior and cocaine-associated cue-induced cocaine-seeking behavior in rats. Although MFZ 10-7 and MTEP lowered the rate of oral sucrose self-administration

  they did not alter total sucrose intake. Further

  MFZ 10-7 appeared to be more potent than MTEP in inducing downward shifts in the cocaine dose-response curve

  but less effective than MTEP in attenuating sucrose-induced reinstatement of sucrose-seeking behavior. MFZ 10-7 and MTEP had no effect on basal locomotor behavior. These findings not only provide additional evidence supporting an important role for mGluR5 in cocaine reward and addiction

  but also introduce a new tool for both in vitro and in vivo investigations with which to further characterize this role.

  A novel mGluR5 antagonist

  MFZ 10-7

  inhibits cocaine-taking and cocaine-seeking behavior in rats

  Abstract\nThe dopamine D3 receptor (D3R) is a target for developing medications to treat substance use disorders. D3R-selective compounds with high affinity and varying efficacies have been discovered

  providing critical research tools for cell-based studies that have been translated to in vivo models of drug abuse. D3R antagonists and partial agonists have shown especially promising results in rodent models of relapse-like behavior

  including stress-

  drug-

  and cue-induced reinstatement of drug seeking. However

  to date

  translation to human studies has been limited. Herein

  we present an overview and illustrate some of the pitfalls and challenges of developing novel D3R-selective compounds toward clinical utility

  especially for treatment of cocaine abuse. Future research and development of D3R-selective antagonists and partial agonists for substance abuse remains critically important but will also require further evaluation and development of translational animal models to determine the best time in the addiction cycle to target D3Rs for optimal therapeutic efficacy.

  Identifying Medication Targets for Psychostimulant Addiction: Unraveling the Dopamine D3 Receptor Hypothesis

  Jeff Bronstein

  Trung Vu

  Andrew Charles

  Luis Beltran-Parrazal

  Am J Physiol Cell Physiol. 2006. 291(4):C687-98\n\nK+ channels are differentially expressed throughout oligodendrocyte (Olg) development. KV1 family voltage-sensitive K+ channels have been implicated in proliferation and migration of Olg progenitor cell (OPC) stage

  and inward rectifier K+ channels (KIR)4.1 are required for OPC differentiation to myelin-forming Olg. In this report we have identified a Shaw family K+ channel

  KV3.1

  that is involved in proliferation and migration of OPC and axon myelination. Application of anti-KV3.1 antibody or knockout of Kv3.1 gene decreased the sustained K+ current component of OPC by 50% and 75%

  respectively. In functional assays block of KV3.1-specific currents or knockout of Kv3.1 gene inhibited proliferation and migration of OPC. Adult Kv3.1 gene-knockout mice had decreased diameter of axons and decreased thickness of myelin in optic nerves compared with age-matched wild-type littermates. Additionally

  KV3.1 was identified as an associated protein of Olg-specific protein (OSP)/claudin-11 via yeast two-hybrid analysis

  which was confirmed by coimmunoprecipitation and coimmunohistochemistry. In summary

  the KV3.1 K+ current accounts for a significant component of the total K+ current in cells of the Olg lineage and

  in association with OSP/claudin-11

  plays a significant role in OPC proliferation and migration and myelination of axons.\n\nAm J Physiol Cell Physiol. 2006 Oct;291(4):C687-98. Epub 2006 Apr 19.\ndoi: 10.​1152/​ajpcell.​00510.​2005

  K+ channel Kv3.1 associates with OSP/claudin-11 and regulates oligodendrocyte development and myelination

  David K. Grandy

  Charles C. Jimenez

  Katherine L. Suchland

  Pharmacol Biochem Behav. 2013. 103(4):831-41\n\nAn allele of the human dopamine D4 receptor (D4R) gene (DRD4)...has been reproducibly found in novelty seekers

  substance abusers

  and individuals with attention-deficit hyperactivity disorder. One hypothesis predicts the resultant protein product of the DRD4.7 polymorphism is deficient in G protein-coupled signaling. If attenuated D4R signaling contributes to these complex behaviors

  then wild-type (WT) mice and mice completely lacking D4Rs (D4R KO) might be expected to display significantly different behavioral responses to stimuli known to affect dopamine signaling

  such as novelty or psychostimulants. Adolescent male D4R KO mice exhibited greater locomotor activity and spent less time in the anxiogenic center of a novel open field environment than WT littermates. The presence of D4Rs had no effect on emergence into a novel environment from a sheltered space or exploration of a novel object. Low doses of acute methylphenidate (MP) had no effect on the exploration of a novel object

  but dose-dependently increased the latency to emerge into a novel environment...WT and D4R KO mice responded differently to high doses of acute MP

  displaying significantly elevated locomotor activity and reduced stereotypy...Chronic MP produced enhanced locomotor sensitization in D4R KO mice

  however this effect could not be fully recapitulated using the putative D4R antagonist L-745-870. These studies suggest that the roles of D4R signaling in novelty-seeking behaviors and the response to psychostimulants are not as clear as previously reported

  and that some of these effects may be due to developmental compensatory effects as a consequence of lost D4R expression. If the DRD4.7 variant results in deficient D4R signaling in vivo

  this may contribute to an elevated risk of sensitization to drugs of abuse including psychostimulants used to treat ADHD.\n\nhttp://dx.doi.org/10.1016/j.pbb.2012.12.006

  Dopamine D4 Receptor Deficiency in Mice Alters Behavioral Responses to Anxiogenic Stimuli and the Psychostimulant Methylphenidate

  Lei Shi

  Caitlin Burzynski

  Adv Pharmacol. 2014. 69:267-300\n\nThe dopamine D3 receptor is a target of pharmacotherapeutic interest in a variety of neurological disorders including schizophrenia

  restless leg syndrome

  and drug addiction. The high protein sequence homology between the D3 and D2 receptors has posed a challenge to developing D3 receptor-selective ligands whose behavioral actions can be attributed to D3 receptor engagement

  in vivo. However

  through primarily small-molecule structure-activity relationship (SAR) studies

  a variety of chemical scaffolds have been discovered over the past two decades that have resulted in several D3 receptor-selective ligands with high affinity and in vivo activity. Nevertheless

  viable clinical candidates remain limited. The recent determination of the high-resolution crystal structure of the D3 receptor has invigorated structure-based drug design

  providing refinements to the molecular dynamic models and testable predictions about receptor-ligand interactions. This chapter will highlight recent preclinical and clinical studies demonstrating potential utility of D3 receptor-selective ligands in the treatment of addiction. In addition

  new structure-based rational drug design strategies for D3 receptor-selective ligands that complement traditional small-molecule SAR to improve the selectivity and directed efficacy profiles are examined.

  Beyond Small-Molecule SAR: Using the Dopamine D3 Receptor Crystal Structure to Guide Drug Design.

  Barbara Slusher

  Jonathan Javitch

  Prashant Donthamsetti

  Elie Pommier

  Caitlin Burzynski

  The dopamine D3 receptor (D3R) is a promising target for the development of pharmacotherapeutics to treat substance use disorders. Several D3R-selective antagonists are effective in animal models of drug abuse

  especially in models of relapse. Nevertheless

  poor bioavailability

  metabolic instability

  and/or predicted toxicity have impeded success in translating these drug candidates to clinical use. Herein

  we report a series of D3R-selective 4-phenylpiperazines with improved metabolic stability. A subset of these compounds was evaluated for D3R functional efficacy and off-target binding at selected 5-HT receptor subtypes

  where significant overlap in SAR with D3R has been observed. Several high affinity D3R antagonists

  including compounds 16 (Ki = 0.12 nM) and 32 (Ki = 0.35 nM)

  showed improved metabolic stability compared to the parent compound

  PG648 (6). Notably

  16 and the classic D3R antagonist SB277011A (2) were effective in reducing self-administration of heroin in wild-type but not D3R knockout mice.

  High Affinity Dopamine D3 Receptor (D3R)-Selective Antagonists Attenuate Heroin Self-Administration in Wild-Type but not D3R Knockout Mice.

  Barbara S. Slusher

  Rana Rais

  Jeffrey R. Deschamps

  Martin Moore

  Caitlin Burzynski

• 2

  The dopamine D3 receptor (D3R) is a target of pharmacotherapeutic interest in a variety of neurological disorders including schizophrenia

  Parkinson's disease

  restless leg syndrome

  and drug addiction. A common molecular template used in the development of D3R-selective antagonists and partial agonists incorporates a butylamide linker between two pharmacophores

  a phenylpiperazine moiety and an extended aryl ring system. The series of compounds described herein incorporates a change to that chemical template

  replacing the amide functional group in the linker chain with a 1

  3-triazole group. Although the amide linker in the 4-phenylpiperazine class of D3R ligands has been previously deemed critical for high D3R affinity and selectivity

  the 1

  3-triazole moiety serves as a suitable bioisosteric replacement and maintains desired D3R-binding functionality of the compounds. Additionally

  using mouse liver microsomes to evaluate CYP450-mediated phase I metabolism

  we determined that novel 1

  3-triazole-containing compounds modestly improves metabolic stability compared to amide-containing analogues. The 1

  3-triazole moiety allows for the modular attachment of chemical subunit libraries using copper-catalyzed azide-alkyne cycloaddition click chemistry

  increasing the range of chemical entities that can be designed

  synthesized

  and developed toward D3R-selective therapeutic agents.

  Using click chemistry toward novel 1

  3-triazole-linked dopamine D3 receptor ligands

  Shaomeng Wang

  Beth Levant

  Cheng Jiang

  Jianyong Chen

  J Med Chem.

  J Med Chem. 2014. 57(11):4962-8\n\nWe report a class of potent and selective dopamine D3 receptor antagonists based upon tranylcypromine. Although tranylcypromine has a low affinity for the rat D3 receptor with low affinity (Ki = 12.8 µM)

  our efforts have yielded (1R

  2S)-11 (CJ-1882)

  which has Ki values of 2.7 nM and 2.8 nM at the rat and human dopamine D3 receptors

  respectively

  and displays selectivities of >10

  000-fold and 223-fold over the rat and human D2 receptors

  respectively. Evaluation in a β-arrestin functional assay showed that (1R

  2S)-11 is a potent and competitive antagonist at the human D3 receptor.

  Tranylcypromine Substituted cis-Hydroxycyclobutylnaphthamides as Potent and Selective Dopamine D3 Receptor Antagonists

  Jeffery R. Deschamps

  Jianjing Cao

  Erick G. Garcia

  ACS Med Chem Lett. 2014.5(6):647-51\n\nThe improved chiral synthesis of the selective dopamine D3 receptor (D3R) antagonist (R)-N-(4-(4-(2

  3-dichlorophenyl)piperazin-1-yl)-3-hydroxybutyl)1H-indole-2-carboxamide ((R)-PG648) is described. The same chiral secondary alcohol intermediate was used to prepare the enantiomers of a 3-F-benzofuranyl analogue

  BAK 2-66. The absolute configurations of the 3-F enantiomers were assigned from their X-ray crystal structures that confirmed retention of configuration during fluorination with N

  N-diethylaminosulfur trifluoride (DAST). (R)-BAK2-66 showed higher D3R affinity and selectivity than its (S)-enantiomer; however

  it had lower D3R affinity and enantioselectivity than (R)-PG648. Further

  importance of the 4-atom linker length between the aryl amide and 4-phenylpiperazine was demonstrated with the 4-fluorobutyl-product (8).

  Chiral Resolution and Serendipitous Fluorination Reaction for the Selective Dopamine D3 Receptor Antagonist BAK2-66

  Eliot L. Gardner

  Ratika Srivastava

  Hai-Ying Zhang

  Yong Huang

  Guo-Hua Bi

  Hong-Ju Yang

  Psychopharmacology (Berl). 2013. 229(2):253-65\n\nRationale The metabotropic glutamate receptor subtype 5 (mGluR5) has been reported to be critically involved in drug reward and addiction. Because the mGluR5 negative allosteric modulators (NAMs) MPEP and MTEP significantly inhibit addictive-like behaviors of cocaine and other drugs of abuse in experimental animals

  it has been suggested that mGluR5 NAMs may have translational potential for treatment of addiction in humans. However

  neither MPEP nor MTEP have been evaluated in humans due to their off-target actions and rapid metabolism.\nObjectives Herein

  we evaluate a potential candidate for translational addiction research: a new sulfate salt formulation of fenobam

  a selective mGluR5 NAM that has been investigated in humans.\nResults In rats

  fenobam sulfate had superior pharmacokinetics compared to the free base

  with improved Cmax (maximal plasma concentration) and longer half life. Oral (p.o.) administration of fenobam sulfate (30 or 60 mg/kg) inhibited intravenous cocaine self-administration

  cocaine-induced reinstatement of drug-seeking behavior and cocaine-associated contextual cue-induced cocaine-seeking behavior in rats. Fenobam sulfate also inhibited oral sucrose self-administration and sucrose-induced reinstatement of sucrose-seeking behavior

  but had no effect on locomotion.\nConclusions This study provides additional support for the role of mGluR5 signaling in cocaine addiction and suggests that fenobam sulfate may have translational potential in medication development for the treatment of cocaine addiction in humans.\n\nDOI: 10.1007/s00213-013-3106-9\nEpub: 2013 Apr 25

  Fenobam Sulfate Inhibits Cocaine-Taking and Cocaine-Seeking Behavior in Rats: Implications for Addiction Treatment in Humans

  Mu-Fa Zou

• Drug Testing

  Animal Models

  Behavioral Neuroscience

  Medicinal Chemistry

  Cell Culture

  In Vivo

  In Vitro

  Immunohistochemistry

  Molecular Biology

  Pharmacology

  Immunofluorescence

  Neuroscience

  GPCRs

  Western Blotting

  PCR

  Drug Discovery

  Microarray Analysis

  Research

  Drug Design

  Cell

  Interferon regulatory factor 3 is necessary for induction of antiviral genes during human cytomegalovirus infection

  Jay A. Nelson

  Scott G. Hansen

  Victor R. DeFilippis

  J Virol.

  J Virol. 2006. 80(2):1032-7\n\nViral infection activates interferon regulatory factor 3 (IRF3)

  a cofactor for the induction of interferon-stimulated genes (ISGs). The role of IRF3 in the activation of ISGs by human cytomegalovirus (HCMV) is controversial despite the fact that HCMV has consistently been shown to induce ISGs during infection of fibroblasts. To address the function of IRF3 in HCMV-mediated ISG induction

  we monitored ISG expression and global gene expression in HCMV-infected cells in which IRF3 function had been depleted by small interfering RNA or blocked by dominant negative IRF3. A specific reduction of ISG induction was observed

  whereas other transcripts were unaffected. We therefore conclude that IRF3 specifically regulates ISG induction during the initial phase of HCMV infection.\n\nJ Virol. 2006 Jan;80(2):1032-7.\ndoi: 10.1128/​JVI.80.2.1032-1037.2006

  Interferon regulatory factor 3 is necessary for induction of antiviral genes during human cytomegalovirus infection