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Vice-ChairDirector of Undergraduate StudiesProfessor of Microbiology
Office: 3-432 BSBIowa City, IA 52242
Office Phone: 319-335-9958
Lab: 3-401 BSBIowa City, IA 52242
BA, Biology/Chemistry, Lawrence UniversityPhD, Cell and Developmental Biology, Harvard University
Post Doctoral, Virology, University of Chicago
Biosciences Graduate ProgramDepartment of Microbiology Graduate ProgramInterdisciplinary Graduate Program in Translational BiomedicineMedical Scientist Training Program
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 for Gene Therapy of Cystic Fibrosis and other Genetic DiseasesHelen C. Levitt Center for Viral PathogenesisHolden Comprehensive Cancer Center
Bone marrow stromal cell antigen 2 (BST-2) restricts mouse mammary tumor virus (MMTV) replication in vivo.
2012 January 27. 9:10.
Intragenic and extragenic suppression of a mutation in herpes simplex virus 1 UL34 that affects both nuclear envelope targeting and membrane budding.
2011 November. 85(22):11615-25.
A functional role for TorsinA in herpes simplex virus 1 nuclear egress.
2011 October. 85(19):9667-79.
Herpes simplex virus 1 pUL34 plays a critical role in cell-to-cell spread of virus in addition to its role in virus replication.
2011 July. 85(14):7203-15.
Significance of host cell kinases in herpes simplex virus type 1 egress and lamin-associated protein disassembly from the nuclear lamina.
2010 October 10. 406(1):127-37.
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.
2010 April. 84(8):3921-34.
Emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-infected cells in a manner dependent on both UL34 and US3.
2007 October. 81(19):10792-803.
Roles for herpes simplex virus type 1 UL34 and US3 proteins in disrupting the nuclear lamina during herpes simplex virus type 1 egress.
2006 April 10. 347(2):261-76.
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.
2004 June. 78(11):5591-600.
Herpes simplex virus type 1 U(L)34 gene product is required for viral envelopment.
2000 January. 74(1):117-29.
Date Last Modified: 08/26/2013 -
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