Zsolt Toth, Ph.D
Department of Oral Biology
1395 Center Drive
Gainesville, FL 32610-0424
- Assistant Professor of Research, University of Southern California, Los Angeles, 2013-2016
- Postdoctoral Research Associate, University of Southern California, Los Angeles, 2008-2013
- Postdoctoral Fellow, Salk Institute, La Jolla, California, 2007
- PhD, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany, 2006
- MSc, University of Szeged, Szeged, Hungary, 2002
Epigenetic regulation of oncogenic herpesvirus infection
My laboratory investigates how Kaposi’s sarcoma-associated herpesvirus (KSHV) can hijack components of the host epigenetic machinery and utilize them to establish persistent infection and cause cancers in humans. KSHV is responsible for the development of the vascular tumor Kaposi’s sarcoma (KS), and two B cell lymphomas such as primary effusion lymphoma and a subset of multicentric Castleman’s disease in immunocompromised people. KSHV is a true oral herpesvirus, which is shed in the oral cavity, and KSHV infection can lead to the development of oral KS, the most common oral malignancy in AIDS patients. Oral epithelial cells have been shown to support lytic replication following primary infection and significant amount of transmissible infectious virions can be detected in saliva of KSHV-positive individuals. Following replication in oral epithelial cells, KSHV may be transmitted into endothelial cells and B lymphocytes where it establishes latency, which is responsible for the life-long infection of the host.
Our goal is to understand the key differences in the epigenetic regulation of the KSHV genome and host genes in the different human cell types, which can determine the outcome of infection (latency or lytic replication). Better understanding of what viral and host epigenetic factors control KSHV infection can lead to the development of novel strategies to blocking KSHV infection and pathogenesis. Our research program uses genetically-engineered KSHV mutants and structural-functional biochemical assays combined with system biology and genomic approaches to interrogate the function of specific viral and host factors that are critical for the persistent KSHV infection and KSHV-induced oncogenesis.
The major research areas of the lab are the following:
(I) Molecular genetic analysis of the KSHV genome to determine what viral cis- and trans-factors regulate the chromatin structure of the KSHV genome in the different phases of KSHV life cycle such as during de novo infection, latency, and lytic reactivation.
(II) Identifying and characterizing the function of cellular histone-modifying enzyme complexes that control the establishment of KSHV latency and lytic reactivation.
(III) Using system biology approaches in collaboration with Dr. Bernadett Papp (Department of Oral Biology), we want to determine what changes in the host epigenome and transcriptome that are induced by KSHV factors are crucial for KSHV replication and cell reprogramming involved in KSHV pathogenesis.
(IV) Understanding what makes oral epithelial cells susceptible to support lytic replication of KSHV following de novo infection compared to other cell types.
- Toth Z, Papp B, Brulois KF, Choi YJ, Gao SJ and Jung JU (2016) LANA-mediated recruitment of host Polycomb Repressive Complexes onto the KSHV genome during de novo infection. PLoS Pathogens, 12(9): e10058788
- Brulois KF, Wong LY, Lee HR, Sivadas P, Ensser A, Feng P, Gao SJ, Toth Z and Jung JU (2015) The association of Kaposi’s sarcoma-associated herpesvirus ORF31 with ORF34 and ORF24 is critical for late gene expression. Journal of Virology, 89(11): 6148-54
- Brulois KF, Toth Z, Wong LY, Feng P, Gao SJ, Ensser A and Jung JU (2014) KSHV K3 and K5 ubiquitin E3 ligases have stage-specific immune evasion roles during lytic replication. Journal of Virology, 88(16):9335-49
- Lee HR, Doğanay S, Chung B, Toth Z, Brulois K, Lee S, Kanketayeva Z, Feng P, Ha TJ and Jung JU. (2014) Kaposi’s Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 4 (vIRF4) targets expression of cellular IRF4 and the Myc gene to facilitate lytic replication. Journal of Virology, 88(4): 2183-94
- Toth Z, Brulois KF, Lee HR, Izumiya Y, Tepper C, Kung HJ, Jung JU. (2013) Biphasic euchromatin-to-heterochromatin transition on the KSHV genome following de novo infection. PLoS Pathogens. December 9(12): e1003813.
- Toth Z, Brulois K and Jung JU. (2013) Kaposi’s sarcoma-associated herpesvirus: biology of a human tumor virus. In Encyclopedia of Human Biology, (Eds: Simon M and Abelson J). Book chapter.
- Toth Z, Brulois K and Jung JU. (2013) The chromatin landscape of Kaposi’s sarcoma-associated herpesvirus. Viruses. 5(5): 1346-73. Review.
- Wong LY, Toth Z, Brulois KF, Inn KS, Lee SH, Lee HR and Jung JU. (2013) Molecular mimicry by γ-2 herpesviruses to modulate host signaling pathways. In: Primates, Pathogens, and Evolution. Developments in Primatology: Progress and Prospects. Vol. 38, Springer Science and Business Media, New York. Book chapter
- Wong LY, Brulois KF, Toth Z, Lee SH, Inn KS, O’Brien K, Lee HR, Cesarman E Jung JU. (2013) KSHV K4.2 immediate early gene product regulates immunoglobulin secretion and calcium homeostasis by interacting with and inhibiting pERP1. Journal of Virology, 87(22): 12069-79
- Lee SH, Toth Z, Wong LY, Brulois K, Nguyen J, Lee JY, Zandi E, Jung JU. (2012) Novel Phosphorylations of IKKγ/NEMO. MBio, 3(6):e00411-12
- Toth, Z., Brulois K, Wong LY, Lee HR, Chung B, and Jung JU. (2012) NELF-mediated suppression of RNA polymerase II elongation of Kaposi’s sarcoma-associated herpesvirus lytic gene expression. Journal of Virology, (86)18: 9696-707
- Brulois KF, Chang H, Lee AS, Ensser A, Wong LY, Toth Z, Lee SH, Lee HR, Myoung J, Ganem D, Oh TK, Kim JF, Gao SJ, and Jung JU. (2012) Construction and manipulation of a new Kaposi’s sarcoma-associated herpesvirus Bacterial artificial chromosome clone. Journal of Virology, (86)18: 9708-20
- He M, Zhang W, Bakken T, Schutten M, Toth Z, Jung JU, Gill P, Cannon M, and Gao SJ. (2012) Cancer Angiogenesis Induced by Kaposi Sarcoma-Associated Herpesvirus Is Mediated by EZH2. Cancer Research, 72: 3582-92
- Lee HR, Choi WC, Lee S, Hwang J, Hwang E, Guchhait K, Haas J, Toth Z, Jeon YH, Oh TK, Kim MH, Jung JU. (2011) Bilateral inhibition of HAUSP deubiquitinase by a viral interferon regulatory factor protein. Nat. Struct. Mol. Biol, 18(12): 1336-44
- Inn KS, Lee SH, Rathbun JY, Wong LY, Toth Z, Machida K, Ou JH, Jung JU. (2011) Inhibition of RIG-I mediated signaling by Kaposi’s sarcoma-associated herpesvirus-encoded deubiquitinase ORF64. Journal of Virology, 85(20): 10899-904
- Jeong JH, Bhatia A, Toth Z, Oh S, Inn KS, Liao CP, Roy-Burman P, Melamed J, Coetzee GA, Jung JU. (2011) TPL2/COT/MAP3K8 (TPL2) activation promotes androgen depletion-independent (ADI) prostate cancer growth. PLoS One 6(1): e16205
- Toth Z, Maglinte DT, Lee SH, Lee HR, Wong LY, Brulois KF, Lee S, Buckley JD, Laird PW, Marquez VE and Jung JU. (2010) Epigenetic analysis of KSHV latent and lytic genomes. PLoS Pathogens 6(7): e1001013
- Lee H, Toth Z, Shin YC, Lee J, Chang H, Gu W, Oh TK, Kim MH and Jung JU. (2009) Kaposi’s sarcoma-associated herpesvirus viral Interferon Regulatory Factor 4 targets MDM2 to deregulate the p53 tumor suppressor pathway. Journal of Virology 83(13): 6739-6747