Abstract

While KSHV can be detected in blood and occasionally in semen, it is frequently secreted in saliva which is believed to be the main route of spread. Nearly 25 years after the identification of KSHV, however, the initial steps in KSHV oral infection and the expressions of host and KSHV genes are still poorly understood. Our main question is: while KSHV establishes latency in most cells and KS lesions by default, why does it lead to spontaneous lytic replication in oral epithelial cells and oral lesions? Our hypothesis is: this difference is due to the differences of viral epigenetics and genomics. As the previous grant has been primarily focused on the epigenetic regulation of KSHV, the current study will characterize the high-order genomic organization of KSHV and investigate the transcriptomic and epigenomic regulations of KSHV at the single cell level using 3D organotypic oral tissue infection model that closely resembles in vivo oral transmission.

Public Health Relevance

The goal of this study is to characterize the high-order genomic organization of KSHV and to investigate the transcriptomic and epigenomic regulations of KSHV at the single cell level using three-dimensional (3D) organotypic oral tissue infection model that closely resembles in vivo oral transmission. This will provide insights into KSHV oral transmission and complication.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
7R01DE023926-07
Application #
10252377
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Iida, Hiroko
Project Start
2020-09-15
Project End
2024-11-30
Budget Start
2020-09-15
Budget End
2020-11-30
Support Year
7
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

Name
Cleveland Clinic Lerner
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195

  Publications

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:
Gruffaz, Marion; Zhou, Shenghua; Vasan, Karthik et al. (2018) Repurposing Cytarabine for Treating Primary Effusion Lymphoma by Targeting Kaposi's Sarcoma-Associated Herpesvirus Latent and Lytic Replications. MBio 9:
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
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
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
Zhu, Ying; Ramos da Silva, Suzane; He, Meilan et al. (2016) An Oncogenic Virus Promotes Cell Survival and Cellular Transformation by Suppressing Glycolysis. PLoS Pathog 12:e1005648
Nicol, Samantha M; Sabbah, Shereen; Brulois, Kevin F et al. (2016) Primary B Lymphocytes Infected with Kaposi's Sarcoma-Associated Herpesvirus Can Be Expanded In Vitro and Are Recognized by LANA-Specific CD4+ T Cells. J Virol 90:3849-3859
Lee, Hye-Ra; Choi, Un Yung; Hwang, Sung-Woo et al. (2016) Viral Inhibition of PRR-Mediated Innate Immune Response: Learning from KSHV Evasion Strategies. Mol Cells 39:777-782
Lee, Myung-Shin; Yuan, Hongfeng; Jeon, Hyungtaek et al. (2016) Human Mesenchymal Stem Cells of Diverse Origins Support Persistent Infection with Kaposi's Sarcoma-Associated Herpesvirus and Manifest Distinct Angiogenic, Invasive, and Transforming Phenotypes. MBio 7:e02109-15

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