A hallmark of KSHV infection is that the virus persists, and causes disease, by disabling aspects of its host's anti-viral innate and adaptive immune responses. Understanding how the virus manipulates its host in this way will be vital to developing effective therapies against this human pathogen. Studies of KSHV infection in an in vivo model are therefore an essential aspect of the research to be addressed by this Program Project. The role of the Genetic Core will be to oversee the development and customization of a humanized NSG mouse model of KSHV infection, which will enable in vivo studies of KSHV infection, persistence and pathogenicity. The Core will initially evaluate different KSHV infection routes, to identify the optimal way to obtain persistent infection, and will establish appropriate assays to monitor KSHV infection levels (lytic and latent gene expression), and to analyze the effect of infections on human cells and hematopoiesis. The Core will provide the technical expertise and training to infect and analyze humanized mice, thereby facilitating studies of the different KSHV mutants that will be generated by each of the Projects and The Virology Core. Finally, the Core will provide the capability to engineer the human cell components of humanized mice prior to engraftment, using lentiviral vectors expressing shRNAs or mRNA nucleofection of TALENs, in order to address questions about the role of human proteins, miRNAs and specific pathways in KSHV infection.

Public Health Relevance

KSHV disease occurs in the context of complex interactions between the virus and its human host, which can only be fully recapitulated in an in vivo model. The use of humanized mice will advance research into the pathogenicity of KSHV, since the model combines KSHV infection of human cells, with the capability to genetically manipulate both the virus and the host, in order to address the hypotheses generated in this Program Project.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Southern California
Los Angeles
United States
Zip Code
Liang, Qiming; Wei, Dahai; Chung, Brian et al. (2018) Novel Role of vBcl2 in the Virion Assembly of Kaposi's Sarcoma-Associated Herpesvirus. J Virol 92:
Foo, Suan-Sin; Chen, Weiqiang; Chan, Yen et al. (2018) Biomarkers and immunoprofiles associated with fetal abnormalities of ZIKV-positive pregnancies. JCI Insight 3:
Zhang, Junjie; Zhao, Jun; Xu, Simin et al. (2018) Species-Specific Deamidation of cGAS by Herpes Simplex Virus UL37 Protein Facilitates Viral Replication. Cell Host Microbe 24:234-248.e5
Foo, Suan-Sin; Chen, Weiqiang; Chan, Yen et al. (2017) Asian Zika virus strains target CD14+ blood monocytes and induce M2-skewed immunosuppression during pregnancy. Nat Microbiol 2:1558-1570
Yuan, Hongfeng; Tan, Brandon; Gao, Shou-Jiang (2017) Tenovin-6 impairs autophagy by inhibiting autophagic flux. Cell Death Dis 8:e2608
Hwang, Sung-Woo; Kim, DongIk; Jung, Jae U et al. (2017) KSHV-encoded viral interferon regulatory factor 4 (vIRF4) interacts with IRF7 and inhibits interferon alpha production. Biochem Biophys Res Commun 486:700-705
Yuan, Hongfeng; He, Meilan; Cheng, Fan et al. (2017) Tenovin-6 inhibits proliferation and survival of diffuse large B-cell lymphoma cells by blocking autophagy. Oncotarget 8:14912-14924
Zhu, Ying; Li, Tingting; Ramos da Silva, Suzane et al. (2017) A Critical Role of Glutamine and Asparagine ?-Nitrogen in Nucleotide Biosynthesis in Cancer Cells Hijacked by an Oncogenic Virus. MBio 8:
Cheng, Fan; He, Meilan; Jung, Jae U et al. (2016) Suppression of Kaposi's Sarcoma-Associated Herpesvirus Infection and Replication by 5'-AMP-Activated Protein Kinase. J Virol 90:6515-6525
Li, Wan; Yan, Qin; Ding, Xiangya et al. (2016) The SH3BGR/STAT3 Pathway Regulates Cell Migration and Angiogenesis Induced by a Gammaherpesvirus MicroRNA. PLoS Pathog 12:e1005605

Showing the most recent 10 out of 67 publications