Hepatitis B virus (HBV) is the most prevalent human tumor virus. It is estimated that chronic HBV infection causes 1,000,000 cases of liver cancer annually. HBV actively replicates within liver cells to maintain its chronic infection. We work to understand the mechanisms by which HBV replicates in order to identify targets for new therapies. During this last funding period our most significant findings and progress included: (1) learning that HBV genome replication requires complex contributions from the replication template. The genomic RNA and DMA replication intermediates are not passive templates, but proceed through dynamic topologies that guide their own replication;(2) elucidating the involvement of the host cellular multivesicular body pathway in HBV virion production;and (3) conducting the first high throughput genetic screen to systematically identify host genes involved in HBV replication. This present proposal will build upon progress engendered during the last funding period. This project has three aims: (1) to study the synthesis of plus-strand DNA to elucidate (a) the mechanisms of template switching and inhibition of in situ priming, (b) the role of the C-terminus of capsid protein, and (c) the relationship between genome maturation and capsid envelopment;(2) to study the synthesis, accumulation and maintenance of cccDNA;and (3) to study the role of the Rho GTPase pathway in HBV virion production. These studies will uncover new mechanisms of virus replication and identify targets for new and better HBV therapies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA022443-35
Application #
8377339
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
Project End
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
35
Fiscal Year
2012
Total Cost
$362,801
Indirect Cost
$115,969
Name
University of Wisconsin Madison
Department
Type
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Zumwalde, Nicholas A; Sharma, Akshat; Xu, Xuequn et al. (2017) Adoptively transferred V?9V?2 T cells show potent antitumor effects in a preclinical B cell lymphomagenesis model. JCI Insight 2:
Ma, Shi-Dong; Tsai, Ming-Han; Romero-Masters, James C et al. (2017) Latent Membrane Protein 1 (LMP1) and LMP2A Collaborate To Promote Epstein-Barr Virus-Induced B Cell Lymphomas in a Cord Blood-Humanized Mouse Model but Are Not Essential. J Virol 91:
Bilger, Andrea; Plowshay, Julie; Ma, Shidong et al. (2017) Leflunomide/teriflunomide inhibit Epstein-Barr virus (EBV)- induced lymphoproliferative disease and lytic viral replication. Oncotarget 8:44266-44280
Yang, Ya-Chun; Liem, Amy; Lambert, Paul F et al. (2017) Dissecting the regulation of EBV's BART miRNAs in carcinomas. Virology 505:148-154
Iwahori, Satoko; UmaƱa, Angie C; VanDeusen, Halena R et al. (2017) Human cytomegalovirus-encoded viral cyclin-dependent kinase (v-CDK) UL97 phosphorylates and inactivates the retinoblastoma protein-related p107 and p130 proteins. J Biol Chem 292:6583-6599
Wille, Coral K; Li, Yangguang; Rui, Lixin et al. (2017) Restricted TET2 Expression in Germinal Center Type B Cells Promotes Stringent Epstein-Barr Virus Latency. J Virol 91:
Chandra, Janin; Kuo, Paula T Y; Hahn, Anne M et al. (2017) Batf3 selectively determines acquisition of CD8+ dendritic cell phenotype and function. Immunol Cell Biol 95:215-223
Pocock, Ginger M; Zimdars, Laraine L; Yuan, Ming et al. (2017) Diverse activities of viral cis-acting RNA regulatory elements revealed using multicolor, long-term, single-cell imaging. Mol Biol Cell 28:476-487
Nowak, Karolin; Linzner, Daniela; Thrasher, Adrian J et al. (2017) Absence of ?-Chain in Keratinocytes Alters Chemokine Secretion, Resulting in Reduced Immune Cell Recruitment. J Invest Dermatol 137:2120-2130
Uberoi, Aayushi; Lambert, Paul F (2017) Rodent Papillomaviruses. Viruses 9:

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