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)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1)
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University of Southern California
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Rodgers, Mary A; Bowman, James W; Fujita, Hiroaki et al. (2014) The linear ubiquitin assembly complex (LUBAC) is essential for NLRP3 inflammasome activation. J Exp Med 211:1333-47
Yan, Qin; Ma, Xinting; Shen, Chenyou et al. (2014) Inhibition of Kaposi's sarcoma-associated herpesvirus lytic replication by HIV-1 Nef and cellular microRNA hsa-miR-1258. J Virol 88:4987-5000
Brulois, Kevin; Toth, Zsolt; Wong, Lai-Yee et al. (2014) Kaposi's sarcoma-associated herpesvirus K3 and K5 ubiquitin E3 ligases have stage-specific immune evasion roles during lytic replication. J Virol 88:9335-49
Shi, Mude; Cho, Hyelim; Inn, Kyung-Soo et al. (2014) Negative regulation of NF-?B activity by brain-specific TRIpartite Motif protein 9. Nat Commun 5:4820
Zhu, Ying; Huang, Yufei; Jung, Jae U et al. (2014) Viral miRNA targeting of bicistronic and polycistronic transcripts. Curr Opin Virol 7:66-72
Brulois, Kevin; Jung, Jae U (2014) Interplay between Kaposi's sarcoma-associated herpesvirus and the innate immune system. Cytokine Growth Factor Rev 25:597-609
Jones, Tiffany; Ramos da Silva, Suzane; Bedolla, Roble et al. (2014) Viral cyclin promotes KSHV-induced cellular transformation and tumorigenesis by overriding contact inhibition. Cell Cycle 13:845-58
Lee, Myung-Shin; Jones, Tiffany; Song, Dae-Yong et al. (2014) Exploitation of the complement system by oncogenic Kaposi's sarcoma-associated herpesvirus for cell survival and persistent infection. PLoS Pathog 10:e1004412
Full, Florian; Jungnickl, Doris; Reuter, Nina et al. (2014) Kaposi's sarcoma associated herpesvirus tegument protein ORF75 is essential for viral lytic replication and plays a critical role in the antagonization of ND10-instituted intrinsic immunity. PLoS Pathog 10:e1003863
Liang, Qiming; Seo, Gil Ju; Choi, Youn Jung et al. (2014) Crosstalk between the cGAS DNA sensor and Beclin-1 autophagy protein shapes innate antimicrobial immune responses. Cell Host Microbe 15:228-38

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