Human gamma-herpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein Barr virus (EBV) are associated with a variety of cancers. Vaccines against EBV and KSHV would reduce the occurrence of virus-associated cancers. Major challenges to vaccine development for herpesviruses include the immunologically silent nature of latency and the large collections of immune evasion genes encoded by the viruses. Our goal is to understand the interactions between the virus and the host immune response. The knowledge will be utilized to develop new vaccine strategies. This Program will focus the research on KSHV. However, KSHV does not have robust lytic replication or a small animal infection model. To complement the studies in KSHV, this Program will also exploit an experimental model based on a closely related rodent virus, murine gammaherpesvirus 68 (MHV-68, also known as yHV-68, or MuHV-4), for proof of principle experiments. All of the research projects in this Program will investigate the effects of cellular factors on various aspects of viral replication and viral immune evasion mechanisms. Thus, it will be more efficient to organize a core that can provide a centralized, coordinated, and cost-efficient service which includes providing assays, reagents, and expertise on KSHV and MHV-68. Core B will generate and provide recombinant KSHV and MHV-68 viruses. In addition, the Core will provide in vitro cell culture systems and the virological assays with protocols, reagents and controls.

Public Health Relevance

Core B is to provide a centralized, coordinated, and cost-efficient service to serve the central mission of the P01 program: to understand the interactions between the virus and the host innate immune response. The knowledge will provide important foundation for the development of new vaccine strategies to prevent cancers associated with gamma-herpesvirus infection.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA177322-05
Application #
9542241
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
5
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Yau, Edwin H; Rana, Tariq M (2018) Next-Generation Sequencing of Genome-Wide CRISPR Screens. Methods Mol Biol 1712:203-216
Gong, Danyang; Zhang, Tian-Hao; Zhao, Dawei et al. (2018) High-Throughput Fitness Profiling of Zika Virus E Protein Reveals Different Roles for Glycosylation during Infection of Mammalian and Mosquito Cells. iScience 1:97-111
Jain, Prashant; Boso, Guney; Langer, Simon et al. (2018) Large-Scale Arrayed Analysis of Protein Degradation Reveals Cellular Targets for HIV-1 Vpu. Cell Rep 22:2493-2503
Dai, Xinghong; Gong, Danyang; Lim, Hanyoung et al. (2018) Structure and mutagenesis reveal essential capsid protein interactions for KSHV replication. Nature 553:521-525
Du, Yushen; Xin, Li; Shi, Yuan et al. (2018) Genome-wide identification of interferon-sensitive mutations enables influenza vaccine design. Science 359:290-296
Gong, Danyang; Dai, Xinghong; Xiao, Yuchen et al. (2017) Virus-Like Vesicles of Kaposi's Sarcoma-Associated Herpesvirus Activate Lytic Replication by Triggering Differentiation Signaling. J Virol 91:
Yau, Edwin H; Kummetha, Indrasena Reddy; Lichinchi, Gianluigi et al. (2017) Genome-Wide CRISPR Screen for Essential Cell Growth Mediators in Mutant KRAS Colorectal Cancers. Cancer Res 77:6330-6339
Šedý, John R; Balmert, M Olivia; Ware, Brian C et al. (2017) A herpesvirus entry mediator mutein with selective agonist action for the inhibitory receptor B and T lymphocyte attenuator. J Biol Chem 292:21060-21070
Du, Yushen; Chi, Xiumei; Wang, Chong et al. (2017) Quantifying perinatal transmission of Hepatitis B viral quasispecies by tag linkage deep sequencing. Sci Rep 7:10168
Du, Yushen; Zhang, Tian-Hao; Dai, Lei et al. (2017) Effects of Mutations on Replicative Fitness and Major Histocompatibility Complex Class I Binding Affinity Are Among the Determinants Underlying Cytotoxic-T-Lymphocyte Escape of HIV-1 Gag Epitopes. MBio 8:

Showing the most recent 10 out of 26 publications