Abstract

Genetic analysis of the viral genes that contribute to the immortalization of human B-lymphocytes by Epstein-Barr virus (EBV) has been hampered by the lack of a reliable means for testing mutant viruses in the absence of contaminating wild-type virus. Dr. Sugden, in collaboration with his longstanding colleague, Dr. Hammerschmidt have developed derivatives of EBV, termed mini-EBVs, that can be propagated as plasmids in E. coli, packaged in a human cell line containing an EBV helper virus, and are capable alone of immortalizing B-lymphocytes. Defined mutations can be introduced into mini-EBVs in their E. coli host. Drs.Sugden and Hammerschmidt propose to measure the effects of defined mutations in selected EBV immortalizing genes on the efficiency of immortalization. These genes will also be analyzed to determine whether they are required for the initiation and/or the maintenance of immortalization. Finally, mini EBVs containing the minimal amount of genetic information required for immortalization will be constructed.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA070723-03
Application #
2712784
Study Section
Virology Study Section (VR)
Program Officer
Wong, May
Project Start
1996-08-15
Project End
2001-05-31
Budget Start
1998-06-01
Budget End
1999-05-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

Chiu, Ya-Fang; Sugden, Bill (2018) Plasmid Partitioning by Human Tumor Viruses. J Virol 92:
Albanese, Manuel; Tagawa, Takanobu; Buschle, Alexander et al. (2017) MicroRNAs of Epstein-Barr Virus Control Innate and Adaptive Antiviral Immunity. J Virol 91:
Chiu, Ya-Fang; Sugden, Arthur U; Fox, Kathryn et al. (2017) Kaposi's sarcoma-associated herpesvirus stably clusters its genomes across generations to maintain itself extrachromosomally. J Cell Biol 216:2745-2758
Albanese, Manuel; Tagawa, Takanobu; Bouvet, Mickaël et al. (2016) Epstein-Barr virus microRNAs reduce immune surveillance by virus-specific CD8+ T cells. Proc Natl Acad Sci U S A 113:E6467-E6475
Tagawa, Takanobu; Albanese, Manuel; Bouvet, Mickaël et al. (2016) Epstein-Barr viral miRNAs inhibit antiviral CD4+ T cell responses targeting IL-12 and peptide processing. J Exp Med 213:2065-80
Chiu, Ya-Fang; Sugden, Bill (2016) Epstein-Barr Virus: The Path from Latent to Productive Infection. Annu Rev Virol 3:359-372
Chakravorty, Adityarup; Sugden, Bill (2015) The AT-hook DNA binding ability of the Epstein Barr virus EBNA1 protein is necessary for the maintenance of viral genomes in latently infected cells. Virology 484:251-8
Hammerschmidt, Wolfgang (2015) The Epigenetic Life Cycle of Epstein-Barr Virus. Curr Top Microbiol Immunol 390:103-17
Steinbrück, Lisa; Gustems, Montse; Medele, Stephanie et al. (2015) K1 and K15 of Kaposi's Sarcoma-Associated Herpesvirus Are Partial Functional Homologues of Latent Membrane Protein 2A of Epstein-Barr Virus. J Virol 89:7248-61
Sugden, Bill (2014) Epstein-Barr virus: the path from association to causality for a ubiquitous human pathogen. PLoS Biol 12:e1001939

Showing the most recent 10 out of 62 publications