Stephen A. Rice, PhD

Associate Professor, Department of Microbiology and Immunology

Stephen A. Rice

Contact Info

ricex019@umn.edu

Office Phone 612-626-4183

Fax 612-626-0623

Lab Phone 612-624-9934

Office Address:
1-115 MRF
689 23rd Ave SE
Minneapolis, MN 55455

Mailing Address:
Department of Microbiology and Immunology
UM Delivery Code: 2821A
1-115 Microbiology Research Facility (MRF)
689 23rd Avenue S.E.
Minneapolis, MN 55455-1507

PhD, University of Utah, 1985

Summary

Expertise

Herpes simplex virus gene expression

Research

Research Summary/Interests

Herpes simplex virus gene expression

The infection of mammalian cells with herpes simplex virus type 1 (HSV-1) results in dramatic alterations to the host cell nucleus, so that viral genes are expressed at high levels, while cellular genes are nearly completely suppressed. This genetic subversion is accomplished by a small set of HSV-1 regulatory proteins, which are amenable to biochemical and genetic analysis. Currently, our laboratory is studying two of these proteins, ICP27 and ICP22. ICP27 is conserved in all known herpesviruses and is absolutely essential for HSV-1 late gene expression. Although its mechanism of action is unknown, a variety of evidence suggests that it is an unusual type of gene regulator which affects pre-mRNA processing and transport. Consistent with its suspected post-transcriptional role, we have shown that ICP27 is an RNA-binding protein that continuously shuttles between the nucleus and cytoplasm. We are also studying ICP22, an HSV-1 protein which is required for viral growth in some cell lines. We have found that HSV-1 infection alters the phosphorylation of the large subunit of RNA polymerase II, and that this effect requires ICP22. Our current goal is to delineate the molecular pathway by which ICP22 alters RNA polymerase II and to understand the functional significance of this change.

Publications

1: Christensen MH, Jensen SB, Miettinen JJ, Luecke S, Prabakaran T, Reinert LS, Mettenleiter T, Chen ZJ, Knipe DM, Sandri-Goldin RM, Enquist LW, Hartmann R, Mogensen TH, Rice SA, Nyman TA, Matikainen S, Paludan SR. HSV-1 ICP27 targets the TBK1-activated STING signalsome to inhibit virus-induced type I IFN expression.

EMBO J. 2016 Jul 1;35(13):1385-99. doi: 10.15252/embj.201593458. PubMed PMID: 27234299; PubMed Central PMCID: PMC4931188.

2: Park D, Lalli J, Sedlackova-Slavikova L, Rice SA. Functional comparison of herpes simplex virus 1 (HSV-1) and HSV-2 ICP27 homologs reveals a role for ICP27 in virion release. J Virol. 2015 Mar;89(5):2892-905. doi: 10.1128/JVI.02994-14.

PubMed PMID: 25540385; PubMed Central PMCID: PMC4325737.

3: Park D, Lengyel J, Rice SA. Role of immediate early protein ICP27 in the differential sensitivity of herpes simplex viruses 1 and 2 to leptomycin B. J Virol. 2013 Aug;87(16):8940-51. doi: 10.1128/JVI.00633-13. PubMed PMID: 23740995;

PubMed Central PMCID: PMC3754045.

4: Rice SA, Davido DJ. HSV-1 ICP22: hijacking host nuclear functions to enhance viral infection. Future Microbiol. 2013 Mar;8(3):311-21. doi: 10.2217/fmb.13.4.

Review. PubMed PMID: 23464370.

5: Horbul JE, Schmechel SC, Miller BR, Rice SA, Southern PJ. Herpes simplex virus-induced epithelial damage and susceptibility to human immunodeficiency virus type 1 infection in human cervical organ culture. PLoS One. 2011;6(7):e22638. doi: 10.1371/journal.pone.0022638. PubMed PMID: 21818356;

PubMed Central PMCID: PMC3144918.

6: Strain AK, Rice SA. Phenotypic suppression of a herpes simplex virus 1 ICP27 mutation by enhanced transcription of the mutant gene. J Virol. 2011 Jun;85(11):5685-90. doi: 10.1128/JVI.00315-11. PubMed PMID: 21411532; PubMed

Central PMCID: PMC3094987.

7: Sedlackova L, Perkins KD, Meyer J, Strain AK, Goldman O, Rice SA. Identification of an ICP27-responsive element in the coding region of a herpes simplex virus type 1 late gene. J Virol. 2010 Mar;84(6):2707-18. doi: 10.1128/JVI.02005-09. PubMed PMID: 20042503; PubMed Central PMCID: PMC2826072.

8: Bastian TW, Livingston CM, Weller SK, Rice SA. Herpes simplex virus type 1 immediate-early protein ICP22 is required for VICE domain formation during productive viral infection. J Virol. 2010 Mar;84(5):2384-94. doi: 10.1128/JVI.01686-09. PubMed PMID: 20032172; PubMed Central PMCID: PMC2820935.

9: Gillis PA, Okagaki LH, Rice SA. Herpes simplex virus type 1 ICP27 induces p38 mitogen-activated protein kinase signaling and apoptosis in HeLa cells. J Virol. 2009 Feb;83(4):1767-77. doi: 10.1128/JVI.01944-08. PubMed PMID: 19073744; PubMed

Central PMCID: PMC2643765.

10: Bastian TW, Rice SA. Identification of sequences in herpes simplex virus type 1 ICP22 that influence RNA polymerase II modification and viral late gene expression. J Virol. 2009 Jan;83(1):128-39. doi: 10.1128/JVI.01954-08. PubMed

PMID: 18971282; PubMed Central PMCID: PMC2612302.

11: Sedlackova, L., K.D. Perkins, J. Lengyel, A.K. Strain, V.L. van Santen, and S. A. Rice. 2008. Herpes simplex virus type 1 ICP27 regulates expression of a variant, secreted form of glycoprotein C by an intron retention mechanism. J. Virol. 82:7443-55.

12: Sedlackova, L. and S.A. Rice. 2008. Herpes simplex virus immediate-early protein ICP27 is required for the efficient virion incorporation of ICP0 and ICP4. J. Virol. 82:268-77.

13: Fraser, K. and S.A. Rice.2007. Herpes simplex virus immediate-early protein ICP22 triggers loss of serine 2-phosphorylated RNA polymerase II. J. Virol. 81:5091-5101.

14: Hargett, D., S.A. Rice, and S. L. Bachenheimer. 2006. Herpes simplex virus type 1 ICP27-dependent activation of NF-kappaB. J. Virol. 80:105665-78.

15: Orlando, J.S., J.W. Balliet, A.S. Kushnir, T.L. Astor, M. Kosz-Vnenchak, S.A. Rice, D.M. Knipe, and P.A. Schaffer. 2006. ICP22 is required for wild-type composition and infectivity of herpes simplex virus type 1 virions. J. Virol. 80:9381-90.

16: Lengyel, J., A. Strain, K. Perkins, and S.A. Rice. 2006. ICP27-dependent resistance of herpes simplex virus type 1 to leptomycin B is associated with enhanced nuclear localization of ICP0 and ICP4. Virology, 352:368-79.

17: Rice, S.A. and K.A. Fraser. 2006. The modification of cellular RNA polymerase II by HSV-1 infection. In Alpha Herpesviruses: Molecular and Cellular Biology. Caister Academic Press.

18: Fraser, K.A. and S.A. Rice.2005. Herpes simplex type 1 infection leads to loss of serine-2 phosphorylation on the carboxyl-terminal domain of RNA polymerase II. J. Virol., 79:11323-34.