Microbiology

Richard J. Roller, PhD

Portrait

Vice-Chair
Director of Undergraduate Studies
Professor of Microbiology

Contact Information

Office: 3-432 BSB
Iowa City, IA 52242
Office Phone: 319-335-9958

Lab: 3-401 BSB
Iowa City, IA 52242
Phone: 319-335-7664

Email: richard-roller@uiowa.edu

Education

BA, Biology/Chemistry, Lawrence University
PhD, Cell and Developmental Biology, Harvard University

Post Doctoral, Virology, University of Chicago

Education/Training Program Affiliations

Biosciences Graduate Program
Department of Microbiology Graduate Program
Interdisciplinary Graduate Program in Translational Biomedicine
Medical Scientist Training Program

Research Summary

The Roller laboratory studies mechanisms of herpesvirus assembly, exit and spread from infected cells.

One goal of research in our laboratory is to understand in detail the process of herpesvirus capsid envelopment at the inner nuclear membrane (INM) with the purpose of using this information for development of antiviral therapies and to advance understanding of the structure and function of the nuclear envelope (NE). This long-term goal can be broken down into the following steps: (i) Identification of the viral and cellular proteins that mediate and regulate envelopment; (ii) Identification of the functions of each of those proteins in envelopment; (iii) Identification of interactions between viral and cellular factors that are critical for envelopment functions; (iv) Characterization of the structures of the essential proteins; (v) Development of assays for therapeutics based on interactions that are essential for envelopment.

We and others have identified essential factors for envelopment and defined functions for some of the critical viral factors. Specifically we have identified specific roles for three viral proteins, pUL34, pUL31 and pUS3 in assembly of a nuclear envelopment complex at the nuclear membrane, in reorganization of the nuclear lamina, and in curvature of the nuclear membrane around the viral capsid. In the process, we have designed and optimized powerful reagents and approaches for study of herpesvirus envelopment. Our goal is to exploit those advantages to further define the functions of the herpesvirus envelopment apparatus, and to begin exploiting the knowledge gained for development of therapeutics based on interference with envelopment interactions.

Herpesviruses cause life-long infections and can cause recurrent disease and shedding in infected people. Recurrence of symptoms and spread of the virus to new hosts requires the ability to spread from the site of latent infection to cells at the periphery and among the cells on the mucosal surface. Amazingly, spread of the virus in recurrent infection occurs in the face of an adaptive immune response, including an antibody response that should neutralize virus released from the cell. The disease-causing properties of these viruses therefore depend on the mechanisms used for spread from cell to cell that protect the virus from exposure to effectors of the immune response.

Spread of the human herpesviruses within the host requires trafficking of newly assembled virus particles from their assembly site at the Golgi to exposed cell surfaces for release to extracellular medium or to cell junctions for cell-to-cell spread (CCS). Neither trafficking pathway is well understood. In part this is because no viral gene functions have been identified that are required for spread trafficking in most cell types. We have discovered that two viral gene products, pUL34 and pUL51, play critical roles in efficient virus release and/or CCS. Both proteins are apparently multifunctional. pUL34 is required for nuclear egress of herpesvirus capsids, and pUL51 has been shown to be required for efficient cytoplasmic assembly of the virus. We have discovered, however, that both proteins play critical roles in release and CCS that can be genetically uncoupled from their roles in virion assembly. Our goal is to understand how these proteins interact with other viral proteins and with cellular membrane trafficking pathways to direct virus particles for spread to an adjacent cell.

Center, Program and Institute Affiliations

Center for Gene Therapy of Cystic Fibrosis and other Genetic Diseases
Helen C. Levitt Center for Viral Pathogenesis
Holden Comprehensive Cancer Center

All Publications

Sen J, Liu X, Roller R, Knipe D.  Herpes simplex virus US3 tegument protein inhibits Toll-like receptor 2 signaling at or before TRAF6 ubiquitination.  Virology.  2013 May 10. 439(2):65-73.
[Link]

Jones P, Maric M, Madison M, Maury W, Roller R, Okeoma C.  BST-2/tetherin-mediated restriction of chikungunya (CHIKV) VLP budding is counteracted by CHIKV non-structural protein 1 (nsP1)..  Virology.  2013 March 30. 438(1):37-49.
[Link]

Chuluunbaatar U, Roller R, Mohr I.  Suppression of extracellular signal-regulated kinase activity in herpes simplex virus 1-infected cells by the Us3 protein kinase.  J Virol.  2012 August. 86(15):7771-6.
[Link]

Jones P, Mehta H, Maric M, Roller R, Okeoma C.  Bone marrow stromal cell antigen 2 (BST-2) restricts mouse mammary tumor virus (MMTV) replication in vivo.  Retrovirology.  2012 January 27. 9:10.
[Link]

Roller R, Haugo A, Kopping N.  Intragenic and extragenic suppression of a mutation in herpes simplex virus 1 UL34 that affects both nuclear envelope targeting and membrane budding.  J Virol.  2011 November. 85(22):11615-25.
[Link]

Maric M, Shao J, Ryan R, Wong C, Gonzalez-Alegre P, Roller R.  A functional role for TorsinA in herpes simplex virus 1 nuclear egress.  J Virol.  2011 October. 85(19):9667-79.
[Link]

Haugo A, Szpara M, Parsons L, Enquist L, Roller R.  Herpes simplex virus 1 pUL34 plays a critical role in cell-to-cell spread of virus in addition to its role in virus replication.  J Virol.  2011 July. 85(14):7203-15.
[Link]

Giri L, Li H, Sandgren D, Feiss M, Roller R, Bonning B, Murhammer D.  Removal of transposon target sites from the Autographa californica multiple nucleopolyhedrovirus fp25k gene delays, but does not prevent, accumulation of the few polyhedra phenotype.  J Gen Virol.  2010 December. 91(Pt 12):3053-64.
[Link]

Chuluunbaatar U, Roller R, Feldman M, Brown S, Shokat K, Mohr I.  Constitutive mTORC1 activation by a herpesvirus Akt surrogate stimulates mRNA translation and viral replication.  Genes Dev.  2010 December 1. 24(23):2627-39.
[Link]

Leach N, Roller R.  Significance of host cell kinases in herpes simplex virus type 1 egress and lamin-associated protein disassembly from the nuclear lamina.  Virology.  2010 October 10. 406(1):127-37.
[Link]

Roller R, Bjerke S, Haugo A, Hanson S.  Analysis of a charge cluster mutation of herpes simplex virus type 1 UL34 and its extragenic suppressor suggests a novel interaction between pUL34 and pUL31 that is necessary for membrane curvature around capsids.  J Virol.  2010 April. 84(8):3921-34.
[Link]

Wisner T, Wright C, Kato A, Kawaguchi Y, Mou F, Baines J, Roller R, Johnson D.  Herpesvirus gB-induced fusion between the virion envelope and outer nuclear membrane during virus egress is regulated by the viral US3 kinase.  J Virol.  2009 April. 83(7):3115-26.
[Link]

Roller R.  Nuclear Egress of Herpesviruses.  Virologica Sinica.  2008. 23:408-15.

Leach N, Bjerke S, Christensen D, Bouchard J, Mou F, Park R, Baines J, Haraguchi T, Roller R.  Emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-infected cells in a manner dependent on both UL34 and US3.  J Virol.  2007 October. 81(19):10792-803.
[Link]

Farnsworth A, Wisner T, Webb M, Roller R, Cohen G, Eisenberg R, Johnson D.  Herpes simplex virus glycoproteins gB and gH function in fusion between the virion envelope and the outer nuclear membrane.  Proc Natl Acad Sci U S A.  2007 June 12. 104(24):10187-92.
[Link]

Bjerke S, Roller R.  Roles for herpes simplex virus type 1 UL34 and US3 proteins in disrupting the nuclear lamina during herpes simplex virus type 1 egress.  Virology.  2006 April 10. 347(2):261-76.
[Link]

Simpson-Holley M, Baines J, Roller R, Knipe D.  Herpes simplex virus 1 U(L)31 and U(L)34 gene products promote the late maturation of viral replication compartments to the nuclear periphery.  J Virol.  2004 June. 78(11):5591-600.
[Link]

Ogg P, McDonell P, Ryckman B, Knudson C, Roller R.  The HSV-1 Us3 protein kinase is sufficient to block apoptosis induced by overexpression of a variety of Bcl-2 family members.  Virology.  2004 February 20. 319(2):212-24.
[Link]

Roller R.  Herpes Simplex Virus Multiprotein Machines as Therapeutic Targets: Progress and Promise.  Chem Tracts.  2004. 17(9):459-85.

Ryckman B, Roller R.  Herpes simplex virus type 1 primary envelopment: UL34 protein modification and the US3-UL34 catalytic relationship.  J Virol.  2004 January. 78(1):399-412.
[Link]

Bjerke S, Cowan J, Kerr J, Reynolds A, Baines J, Roller R.  Effects of charged cluster mutations on the function of herpes simplex virus type 1 UL34 protein.  J Virol.  2003 July. 77(13):7601-10.
[Link]

Reynolds A, Wills E, Roller R, Ryckman B, Baines J.  Ultrastructural localization of the herpes simplex virus type 1 UL31, UL34, and US3 proteins suggests specific roles in primary envelopment and egress of nucleocapsids.  J Virol.  2002 September. 76(17):8939-52.
[Link]

Huber M, Wisner T, Hegde N, Goldsmith K, Rauch D, Roller R, Krummenacher C, Eisenberg R, Cohen G, Johnson D.  Herpes simplex virus with highly reduced gD levels can efficiently enter and spread between human keratinocytes.  J Virol.  2001 November. 75(21):10309-18.
[Link]

Reynolds A, Ryckman B, Baines J, Zhou Y, Liang L, Roller R.  U(L)31 and U(L)34 proteins of herpes simplex virus type 1 form a complex that accumulates at the nuclear rim and is required for envelopment of nucleocapsids.  J Virol.  2001 September. 75(18):8803-17.
[Link]

Rauch D, Rodriguez N, Roller R.  Mutations in herpes simplex virus glycoprotein D distinguish entry of free virus from cell-cell spread.  J Virol.  2000 December. 74(24):11437-46.
[Link]

Roller R, Zhou Y, Schnetzer R, Ferguson J, DeSalvo D.  Herpes simplex virus type 1 U(L)34 gene product is required for viral envelopment.  J Virol.  2000 January. 74(1):117-29.
[Link]

Roller R.  Identification of Bacterial Unknowns by rRNA Sequence Similarity.  American Society for Microbiology;  1999.  Available from: www.microbelibrary.org/library/resources/3908-identification-of-bacterial-unknowns-by-rrna-sequence-similarity

Roller R, Rauch D.  Herpesvirus entry mediator HVEM mediates cell-cell spread in BHK(TK-) cell clones.  J Virol.  1998 February. 72(2):1411-7.
[Link]

Roller R, Herold B.  Characterization of a BHK(TK-) cell clone resistant to postattachment entry by herpes simplex virus types 1 and 2.  J Virol.  1997 August. 71(8):5805-13.
[Link]

Roller R, Monk L, Stuart D, Roizman B.  Structure and function in the herpes simplex virus 1 RNA-binding protein U(s)11: mapping of the domain required for ribosomal and nucleolar association and RNA binding in vitro.  J Virol.  1996 May. 70(5):2842-51.
[Link]

Roller R, Roizman B.  A herpes simplex virus 1 US11-expressing cell line is resistant to herpes simplex virus infection at a step in viral entry mediated by glycoprotein D.  J Virol.  1994 May. 68(5):2830-9.
[Link]

Igarashi K, Fawl R, Roller R, Roizman B.  Construction and properties of a recombinant herpes simplex virus 1 lacking both S-component origins of DNA synthesis.  J Virol.  1993 April. 67(4):2123-32.
[Link]

Kinloch R, Roller R, Wassarman P.  Quantitative analysis of specific messenger RNAs by ribonuclease protection.  Methods Enzymol.  1993. 225:294-303.
[Link]

McCormick L, Roller R, Roizman B.  Characterization of a herpes simplex virus sequence which binds a cellular protein as either a single-stranded or double-stranded DNA or RNA.  J Virol.  1992 June. 66(6):3435-47.
[Link]

Roller R, Roizman B.  The herpes simplex virus 1 RNA binding protein US11 is a virion component and associates with ribosomal 60S subunits.  J Virol.  1992 June. 66(6):3624-32.
[Link]

Roller R, Roizman B.  Herpes simplex virus 1 RNA-binding protein US11 negatively regulates the accumulation of a truncated viral mRNA.  J Virol.  1991 November. 65(11):5873-9.
[Link]

Roller R, Roizman B.  The herpes simplex virus Us11 open reading frame encodes a sequence-specific RNA-binding protein.  J Virol.  1990 July. 64(7):3463-70.
[Link]

Kinloch R, Roller R, Wasserman P.  Organization and expression of the mouse sperm receptor gene.  1990. 125:9-20.

Roller R, McCormick A, Roizman B.  Cellular proteins specifically bind single- and double-stranded DNA and RNA from the initiation site of a transcript that crosses the origin of DNA replication of herpes simplex virus 1.  Proc Natl Acad Sci U S A.  1989 September. 86(17):6518-22.
[Link]

Roller R, Kinloch R, Hiraoka B, Li S, Wassarman P.  Gene expression during mammalian oogenesis and early embryogenesis: quantification of three messenger RNAs abundant in fully grown mouse oocytes.  Development.  1989 June. 106(2):251-61.
[Link]

Wassarman P, Bleil J, Fimiani C, Florman H, Greve J, Kinloch R, Moller C, Mortillo S, Roller R, Salzmann G, Vazquez M.  The mouse egg's receptor for sperm: a multifunctional zona pellucida glycoprotein.  Springer, New York.  1989. 

Kinloch R, Roller R, Fimiani C, Wassarman D, Wassarman P.  Primary structure of the mouse sperm receptor polypeptide determined by genomic cloning.  Proc Natl Acad Sci U S A.  1988 September. 85(17):6409-13.
[Link]

Wassarman P, Bleil J, Fimiani C, Florman H, Greve J, Roller R, Salzmann G, Samuels F, Wenk-Salamone K.  Receptor mediated binding and membrane fusion during sperm-egg interaction in mice.  Alan R. Liss, New York.  1987. 

Wassarman P, Bleil J, Florman H, Greve J, Roller R, Salzmann G.  Nature of the mouse egg's receptor for sperm.  Plenum.  1986. 
[Link]

Wassarman P, Bleil J, Florman H, Greve J, Roller R, Salzmann G.  The mouse egg's extracellular coat: synthesis, structure and function.  Alan R. Liss, New York.  1986. 

Wassarman P, Bleil J, Florman H, Greve J, Roller R, Salzmann G, Samuels F.  The mouse egg's receptor for sperm: what is it and how does it work?.  Cold Spring Harb Symp Quant Biol.  1985. 50:11-9.
[Link]

Roller R, Wassarman P.  Role of asparagine-linked oligosaccharides in secretion of glycoproteins of the mouse egg's extracellular coat.  J Biol Chem.  1983 November 10. 258(21):13243-9.
[Link]

Salzmann G, Greve J, Roller R, Wassarman P.  Biosynthesis of the sperm receptor during oogenesis in the mouse.  EMBO J.  1983. 2(9):1451-6.
[Link]

Greve J, Salzmann G, Roller R, Wassarman P.  Biosynthesis of the major zona pellucida glycoprotein secreted by oocytes during mammalian oogenesis.  Cell.  1982 December. 31(3 Pt 2):749-59.
[Link]

Date Last Modified: 08/26/2013 - 16:19:15