Richard J. Roller, PhD

Portrait
Professor of Microbiology and Immunology
Vice-Chair
Director of Undergraduate Studies

Contact Information

Office
3-432 Bowen Science Building
51 Newton Rd
Iowa City, IA 52242
319-335-9958

Lab
3-401 Bowen Science Building
51 Newton Rd
Iowa City, IA 52242
319-335-7664

Education

BA, Biology/Chemistry, Lawrence University
PhD, Cell and Developmental Biology, Harvard University
Postdoctoral Fellow, Virology, University of Chicago

Education/Training Program Affiliations

Biomedical Science Program, Department of Microbiology Graduate Program, Interdisciplinary Graduate Program in Translational Biomedicine, Medical Scientist Training Program

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

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.

Publications

Baines, J., Roller, R. J. (2017). Herpesvirus Nuclear Egress. Adv Anat Embryol Cell Biol, 223, 143-169. PMID: 28528443.

Vu, A., Poyzer, C. & Roller, R. J. (2016). Extragenic Suppression of a Mutation in Herpes Simplex Virus 1 UL34 That Affects Lamina Disruption and Nuclear Egress. J Virol, 90(23), 10738-10751. PMID: 27654296.

Wu, S., Pan, S., Zhang, L., Baines, J., Roller, R. J., Ames, J., Yang, M., Wang, J., Chen, D., Liu, Y., Zhang, C., Cao, Y. & He, B. (2016). Herpes Simplex Virus 1 Induces Phosphorylation and Reorganization of Lamin A/C through the ?134.5 Protein That Facilitates Nuclear Egress. J Virol, 90(22), 10414-10422. PMID: 27630226.

Roller, R. J., Fetters, R. (2015). The herpes simplex virus 1 UL51 protein interacts with the UL7 protein and plays a role in its recruitment into the virion. J Virol, 89(6), 3112-22. PMID: 25552711.

Madison, M. N., Roller, R. J. & Okeoma, C. M. (2014). Human semen contains exosomes with potent anti-HIV-1 activity. Retrovirology, 11, 102. PMID: 25407601.

Maric, M., Haugo, A. C., Dauer, W., Johnson, D. & Roller, R. J. (2014). Nuclear envelope breakdown induced by herpes simplex virus type 1 involves the activity of viral fusion proteins. Virology, 460-461, 128-37. PMID: 25010278.

Roller, R. J., Haugo, A. C., Yang, K. & Baines, J. D. (2014). The herpes simplex virus 1 UL51 gene product has cell type-specific functions in cell-to-cell spread. J VIrol, 88(8), 4058-68. PMID: 24453372.

Sen, J., Liu, X., Roller, R. J. & Knipe, D. M. (2013). Herpes simplex virus US3 tegument protein inhibits Toll-like receptor 2 signaling at or before TRAF6 ubiquitination. Virology, 439(2), 65-73. PMID: 23478027.

Jones, P. H., Maric, M., Madison, M. N., Maury, W., Roller, R. J. & Okeoma, C. M. (2013). BST-2/tetherin-mediated restriction of chikungunya (CHIKV) VLP budding is counteracted by CHIKV non-structural protein 1 (nsP1). Virology, 438(1), 37-49. PMID: 23411007.

Chuluunbaatar, U., Roller, R. J. & Mohr, I. (2012). Suppression of extracellular signal-regulated kinase activity in herpes simplex virus 1-infected cells by the Us3 protein kinase. J Virol, 86(15), 7771-6. PMID: 22593153.

Jones, P. H., Mehta, H. V., Maric, M., Roller, R. J. & Okeoma, C. M. (2012). Bone marrow stromal cell antigen 2 (BST-2) restricts mouse mammary tumor virus (MMTV) replication in vivo. Retrovirology, 9, 10. PMID: 22284121.

Roller, R. J., Haugo, A. C. & Kopping, N. J. (2011). Intragenic and extragenic suppression of a mutation in herpes simplex virus 1 UL34 that affects both nuclear envelope targeting and membrane budding. J Virol, 85(22), 11615-25. PMID: 21900173.

Maric, M., Shao, J., Ryan, R. J., Wong, C. S., Gonzalez-Alegre, P. & Roller, R. J. (2011). A functional role for TorsinA in herpes simplex virus 1 nuclear egress. J Virol, 85(19), 9667-79. PMID: 21775450.

Haugo, A. C., Szpara, M. L., Parsons, L., Enquist, L. W. & Roller, R. J. (2011). 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, 85(14), 7203-15. PMID: 21561917.

Chuluunbaatar, U., Roller, R. J., Feldman, M. E., Brown, S., Shokat, K. M. & Mohr, I. (2010). Constitutive mTORC1 activation by a herpesvirus Akt surrogate stimulates mRNA translation and viral replication. Genes Dev, 24(23), 2627-39. PMID: 21123650.

Giri, L., Li, H., Sandgren, D., Feiss, M. G., Roller, R. J., Bonning, B. C. & Murhammer, D. W. (2010). 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, 91(Pt 12), 3053-64. PMID: 20810745.

Leach, N. R., Roller, R. J. (2010). Significance of host cell kinases in herpes simplex virus type 1 egress and lamin-associated protein disassembly from the nuclear lamina. Virology, 406(1), 127-37. PMID: 20674954.

Roller, R. J., Bjerke, S. L., Haugo, A. C. & Hanson, S. (2010). 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, 84(8), 3921-34. PMID: 20106917.

Wisner, T. W., Wright, C. C., Kato, A., Kawaguchi, Y., Mou, F., Baines, J. D., Roller, R. J. & Johnson, D. C. (2009). Herpesvirus gB-induced fusion between the virion envelope and outer nuclear membrane during virus egress is regulated by the viral US3 kinase. J Virol, 83(7), 3115-26. PMID: 19158241.

Roller, R. J. (2008). Nuclear Egress of Herpesviruses. Virologica Sinica, 23, 408-15.

Leach, N., Bjerke, S. L., Christensen, D. K., Bouchard, J. M., Mou, F., Park, R., Baines, J., Haraguchi, T. & Roller, R. J. (2007). Emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-infected cells in a manner dependent on both UL34 and US3. J Virol, 81(19), 10792-803. PMID: 17652388.

Farnsworth, A., Wisner, T. W., Webb, M., Roller, R. J., Cohen, G., Eisenberg, R. & Johnson, D. C. (2007). 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, 104(24), 10187-92. PMID: 17548810.

Bjerke, S. L., Roller, R. J. (2006). Roles for herpes simplex virus type 1 UL34 and US3 proteins in disrupting the nuclear lamina during herpes simplex virus type 1 egress. Virology, 347(2), 261-76. PMID: 16427676.

Simpson-Holley, M., Baines, J., Roller, R. J. & Knipe, D. M. (2004). 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, 78(11), 5591-600. PMID: 15140956.

Ogg, P. D., McDonell, P. J., Ryckman, B. J., Knudson, C. M. & Roller, R. J. (2004). The HSV-1 Us3 protein kinase is sufficient to block apoptosis induced by overexpression of a variety of Bcl-2 family members. Virology, 319(2), 212-24. PMID: 14980482.

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

Ryckman, B. J., Roller, R. J. (2004). Herpes simplex virus type 1 primary envelopment: UL34 protein modification and the US3-UL34 catalytic relationship. J Virol, 78(1), 399-412. PMID: 14671121.

Bjerke, S. L., Cowan, J. M., Kerr, J. K., Reynolds, A. E., Baines, J. D. & Roller, R. J. (2003). Effects of charged cluster mutations on the function of herpes simplex virus type 1 UL34 protein. J Virol, 77(13), 7601-10. PMID: 12805460.

Reynolds, A. E., Wills, E. G., Roller, R. J., Ryckman, B. J. & Baines, J. D. (2002). 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, 76(17), 8939-52. PMID: 12163613.

Huber, M. T., Wisner, T. W., Hegde, N. R., Goldsmith, K. A., Rauch, D. A., Roller, R. J., Krummenacher, C., Eisenberg, R. J., Cohen, G. H. & Johnson, D. C. (2001). Herpes simplex virus with highly reduced gD levels can efficiently enter and spread between human keratinocytes. J Virol, 75(21), 10309-18. PMID: 11581399.

Reynolds, A. E., Ryckman, B. J., Baines, J. D., Zhou, Y., Liang, L. & Roller, R. J. (2001). 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, 75(18), 8803-17. PMID: 11507225.

Rauch, D. A., Rodriguez, N. & Roller, R. J. (2000). Mutations in herpes simplex virus glycoprotein D distinguish entry of free virus from cell-cell spread. J Virol, 74(24), 11437-46. PMID: 11090139.

Roller, R. J., Zhou, Y., Schnetzer, R., Ferguson, J. & DeSalvo, D. (2000). Herpes simplex virus type 1 U(L)34 gene product is required for viral envelopment. J Virol, 74(1), 117-29. PMID: 10590098.

Roller, R. J. (1999). Identification of Bacterial Unknowns by rRNA Sequence Similarity. In MicrobeLibrary. American Society for Microbiology.

Roller, R. J., Rauch, D. (1998). Herpesvirus entry mediator HVEM mediates cell-cell spread in BHK(TK-) cell clones. J Virol, 72(2), 1411-7. PMID: 9445042.

Roller, R. J., Herold, B. C. (1997). Characterization of a BHK(TK-) cell clone resistant to postattachment entry by herpes simplex virus types 1 and 2. J Virol, 71(8), 5805-13. PMID: 9223469.

Roller, R. J., Monk, L. L., Stuart, D. & Roizman, B. (1996). 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, 70(5), 2842-51. PMID: 8627758.

Roller, R. J., Roizman, B. (1994). 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, 68(5), 2830-9. PMID: 8151754.

Igarashi, K., Fawl, R., Roller, R. J. & Roizman, B. (1993). Construction and properties of a recombinant herpes simplex virus 1 lacking both S-component origins of DNA synthesis. J Virol, 67(4), 2123-32. PMID: 8383234.

Kinloch, R. A., Roller, R. J. & Wassarman, P. M. (1993). Quantitative analysis of specific messenger RNAs by ribonuclease protection. Methods Enzymol, 225, 294-303. PMID: 8231861.

McCormick, L., Roller, R. J. & Roizman, B. (1992). 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, 66(6), 3435-47. PMID: 1316459.

Roller, R. J., Roizman, B. (1992). The herpes simplex virus 1 RNA binding protein US11 is a virion component and associates with ribosomal 60S subunits. J Virol, 66(6), 3624-32. PMID: 1316472.

Roller, R. J., Roizman, B. (1991). Herpes simplex virus 1 RNA-binding protein US11 negatively regulates the accumulation of a truncated viral mRNA. J Virol, 65(11), 5873-9. PMID: 1656075.

Roller, R. J., Roizman, B. (1990). The herpes simplex virus Us11 open reading frame encodes a sequence-specific RNA-binding protein. J Virol, 64(7), 3463-70. PMID: 2161949.

Kinloch, R. A., Roller, R. J. & Wasserman, P. M. (1990). Organization and expression of the mouse sperm receptor gene.

Roller, R. J., McCormick, A. L. & Roizman, B. (1989). 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, 86(17), 6518-22. PMID: 2549540.

Roller, R. J., Kinloch, R. A., Hiraoka, B. Y., Li, S. S. & Wassarman, P. M. (1989). Gene expression during mammalian oogenesis and early embryogenesis: quantification of three messenger RNAs abundant in fully grown mouse oocytes. Development, 106(2), 251-61. PMID: 2591314.

Wassarman, P., Bleil, J., Fimiani, C., Florman, H., Greve, J., Kinloch, R., Moller, C., Mortillo, S., Roller, R. J., Salzmann, G. & Vazquez, M. (1989). The mouse egg's receptor for sperm: a multifunctional zona pellucida glycoprotein. In J. Dietl (Eds.) The Mammalian Egg Coat. pp. 18-37. Springer, New York.

Kinloch, R. A., Roller, R. J., Fimiani, C. M., Wassarman, D. A. & Wassarman, P. M. (1988). Primary structure of the mouse sperm receptor polypeptide determined by genomic cloning. Proc Natl Acad Sci U S A, 85(17), 6409-13. PMID: 2842770.

Wassarman, P. M., Bleil, J. D., Fimiani, C. M., Florman, H. M., Greve, J. M., Roller, R. J., Salzmann, G. S., Samuels, F. G. & Wenk-Salamone, K. (1987). Receptor mediated binding and membrane fusion during sperm-egg interaction in mice. In R. A. Firtel , E. H. Davidson (Eds.) Molecular Approaches to Developmental Biology. pp. 51-65. Alan R. Liss, New York.

Wassarman, P. M., Bleil, J. D., Florman, H. M., Greve, J. M., Roller, R. J. & Salzmann, G. S. (1986). Nature of the mouse egg's receptor for sperm. In J. L. Hedrick (Eds.) The Molecular and Cellular Biology of Fertilization. pp. 55-77. Plenum. PMID: 3548245.

Wassarman, P. M., Bleil, J. D., Florman, H. M., Greve, J. M., Roller, R. J. & Salzmann, G. S. (1986). The mouse egg's extracellular coat: synthesis, structure and function. In J. G. Gall (Eds.) Gametogenesis and the Early Embryo. pp. 371-88. Alan R. Liss, New York.

Wassarman, P. M., Bleil, J. D., Florman, H. M., Greve, J. M., Roller, R. J., Salzmann, G. S. & Samuels, F. G. (1985). The mouse egg's receptor for sperm: what is it and how does it work?. In J. Sambrook (Eds.) Molecular Biology of Development. pp. 11-9. Cold Spring Harb Symp Quant Biol. PMID: 3006984.

Roller, R. J., Wassarman, P. M. (1983). Role of asparagine-linked oligosaccharides in secretion of glycoproteins of the mouse egg's extracellular coat. J Biol Chem, 258(21), 13243-9. PMID: 6630229.

Salzmann, G. S., Greve, J. M., Roller, R. J. & Wassarman, P. M. (1983). Biosynthesis of the sperm receptor during oogenesis in the mouse. EMBO J, 2(9), 1451-6. PMID: 11892795.

Greve, J. M., Salzmann, G. S., Roller, R. J. & Wassarman, P. M. (1982). Biosynthesis of the major zona pellucida glycoprotein secreted by oocytes during mammalian oogenesis. Cell, 31(3 Pt 2), 749-59. PMID: 6819087.