courtney-galle@uiowa.edu
Mentor: Jeffery Meier, M.D.
Lab Room: Bldg. 41, VAMC
Lab Phone: 319-338-0581

Characterization of the cis-acting elements within the HCMV major immediate-early (MIE) distal enhancer and their function in the regulation of MIE gene expression and viral replication.

Human cytomegalovirus (HCMV) is a beta-herpesvirus that establishes quiescent infection in the majority of adults and can reactivate in the immunocompromised causing life-threatening disease. The HCMV major immediate early (MIE) enhancer/promoter is responsible for driving expression of two gene products, IE1 and IE2, which are required for viral replication. The MIE enhancer contains multiple putative binding sites for transcription factors whose functions are currently unknown. My research focuses on characterizing these transcription factor binding sites and the pathways that utilize them during activation and silencing of the MIE promoter.

Our lab has previously shown that deletion of the distal region of the MIE enhancer significantly reduces gene products and viral replication when at a low multiplicity of infection. The distal enhancer contains multiple GC-rich motifs (TGGGC and GGCGGG), which are thought to bind Sp1 family members. To understand the role these motifs play in regulation I created recombinant HCMVs with all or some of the GC-rich elements mutated and am currently studying their viral replication efficiencies. Through these studies I hope to provide a comprehensive understanding of the regulatory mechanisms underlying productive HCMV infection, which may uncover novel targets for antiviral therapy.

Publications:

Krueger BJ, Jeronimo C, Roy BB, Bouchard A, Barrandon C, Byers SA, Searcey CE, Cooper JJ, Bensaude O, Cohen EA, Coulombe B, Price DH. LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and hnRNP A1 are reversibly associated. Nucleic Acids Res. 2008 Apr;36(7):2219-29. Epub 2008 Feb 16. PMCID: PMC2367717 PMID: 18281698

Yuan J, Liu X, Wu AW, McGonagill PW, Keller MJ, Galle CS, Meier JL. Breaking human cytomegalovirus major immediate-early gene silence by vasoactive intestinal peptide stimulation of the protein kinase A-CREB-TORC2 signaling cascade in human pluripotent embryonal NTera2 cells. J Virol. 2009 Jul;83(13):6391-403. Epub 2009 Apr 15. PubMed PMID: 19369332; PubMed Central PMCID: PMC2698552.

Liu X, Yuan J, Wu AW, McGonagill PW, Galle CS, Meier JL. Phorbol ester-induced human cytomegalovirus major immediate-early (MIE) enhancer activation through PKC-delta, CREB, and NF-kappaB desilences MIE gene expression in quiescently infected human pluripotent NTera2 cells. J Virol. 2010 Sep;84(17):8495-508. Epub 2010 May 26. PubMed PMID: 20504934; PubMed Central PMCID: PMC2919020.

Marquez RT, Wendlandt E, Searcey Galle C, Keck K, McCaffrey AP. microRNA-21 is Upregulated During the Proliferative Phase of Liver Regeneration, Targets Pellino-1 and Inhibits NF-{kappa}B Signaling. Am J Physiol Gastrointest Liver Physiol. 2010 Feb 18. [Epub ahead of print] PubMed PMID: 20167875.

Abstracts:

Galle CS, McGonagill, PW, Tibesar EE, Keller MJ, Vanlerberghe BM, Wu AG, Meier JL. TGGGCA/G- and GC-Box Repeats in the HCMV MIE Enhancer Function in Maintenance of Viral MIE Gene Expression in Acutely Infected Fibroblasts, Talk given at the 6th Biennial All Iowa Virology Symposium, Iowa City Iowa November 6th, 2010

Galle CS, McGonagill, PW, Tibesar EE, Keller MJ, Vanlerberghe BM, Wu AG, Meier JL. Clustering of TGGGC-motifs and GC-boxes in the HCMV MIE Enhancer Drives Viral Gene Expression and Replication in Fibroblasts. Poster presentation at International Herpesvirus Workshop, Salt lake City, Utah July, 2010

Galle CS, McGonagill, PW, Tibesar EE, Keller MJ, Vanlerberghe BM, Wu AG, Meier JL. TGGGCA/G- and GC-Box Repeats in the HCMV MIE Enhancer Function in Maintenance of Viral MIE Gene Expression in Acutely Infected Fibroblasts. Poster at Molecular and Cellular Biology Program Retreat November, 2010

Galle CS, McGonagill, PW, Tibesar EE, Keller MJ, Vanlerberghe BM, Wu AG, Meier JL. GC-Rich repeats in the Human Cytomegalovirus Major Immediate-Early Distal Enhancer Activate Viral Gene Expression and Replication. Poster presentation at Molecular and Cellular Biology Retreat, Amana, IA October, 2008

Galle CS, McGonagill, PW, Tibesar EE, Keller MJ, Vanlerberghe BM, Wu AG, Meier JL. GC-Rich repeats in the Human Cytomegalovirus Major Immediate-Early Distal Enhancer Activate Viral Gene Expression and Replication. Poster presentation at the 5th Biennial All Iowa Virology Symposium, Ames Iowa September 2008