About

Zsolt Toth, Ph.D., serves as an Associate Professor of Oral Biology at the University of Florida College of Dentistry. His research focuses on the mechanisms by which cancer-causing viruses, particularly the Kaposi’s sarcoma–associated herpesvirus (KSHV), establish latency and reactivate, contributing to oral cancers associated with AIDS. Toth's work investigates how KSHV remains dormant within host cells, evades immune detection, and the cellular and viral strategies that promote infection and oncogenesis. His research has uncovered multiple novel cellular factors and viral strategies that influence epigenetic regulation, cellular signaling pathways, and protein stability related to KSHV infection. Toth's lab explores how the virus mimics human cellular proteins to hijack host machinery and how environmental stressors, such as hypoxia and oral bacteria byproducts, impact viral infection outcomes. His work aims to identify intervention points for therapies to prevent transmission and cancer development. Recognized for his significant contributions to oncology and virology, Toth was named a 2026 UFRF Professor, an honor reflecting his research excellence and leadership in his field.

Research topics

• Virology
• Medicine
• Biology
• Immunology
• Genetics
• Political Science
• Pathology
• Cell biology

Selected publications

• Optimizing nitrogen and sulfur supplementation for enhanced growth and biochemical composition in Solanum lycopersicum under hydroponic conditions

  Scientific Reports · 2026-01-18

  articleOpen access

  Solanum lycopersicum (tomato) is a globally significant crop valued for its nutritional and economic importance. This study investigated the effects of nitrogen (N) and sulfur (S) supplementation on tomato growth, biochemical profiles, and stress responses in a hydroponic system. Five treatments were tested: T1 (0% N, 0% S), T2 (50% N, 50% S), T3 (100% N, 100% S, control), T4 (250% N, 250% S), and T5 (500% N, 500% S). Results suggest that T3 (100% N, 100% S) supported optimal growth (plant height: 35.3 cm, leaf number: 33.3, root weight: 1.48 g), while T1 exhibited severe deficiency symptoms and T5 showed signs of nutrient toxicity. Biochemical analyses revealed strong positive correlations between N/S availability and chlorophyll (r = 0.92, p < 0.01), carotenoids (r = 0.89, p < 0.01), and protein content (r = 0.95, p < 0.01). T5 displayed elevated antioxidant enzyme activities (CAT: 0.42 μmol/min/mg protein; APX: 2.40 μmol/min/mg protein) and increased cell death (40.0%), indicating metabolic stress. These findings suggest that the 100% N/S treatment was optimal for tomato growth and biochemical composition in hydroponic systems, while excessive nutrients induce stress. This study highlights the importance of precise nutrient management for sustainable hydroponic tomato production. Limitations include the use of a single cultivar, a small sample size (n = 3), and a controlled hydroponic environment, which may not fully represent field conditions.

  PublisherOA PDFDOI

• Stage-specific regulation of KSHV infection by HIF-1α

  Journal of Virology · 2026-03-10

  articleOpen accessSenior author

  ABSTRACT The impact of physiological stress conditions on Kaposi’s sarcoma-associated herpesvirus (KSHV) infection remains poorly understood. One such stressor, hypoxia, is regulated by the transcription factor HIF-1α. We recently reported that hypoxia, or HIF-1α expression alone, can promote lytic infection in cells that typically support latent infection under normoxia. Here, we show that hypoxia-induced lytic infection is reversible, leading to an abortive lytic cycle if the hypoxic condition ceases. Additionally, we found that HIF-1α induces lytic de novo infection only if expressed within the first 24 h post-infection (hpi). We show that HIF-1α can bind to viral promoters and induce lytic genes only during this early window of infection, before the KSHV genome undergoes heterochromatinization and establishes latency. In contrast, regardless of the timing of HIF-1α expression during KSHV infection, the induction of HIF-1α host target genes remains unaffected. These results indicate that the heterochromatinized KSHV DNA becomes resistant to HIF-1α-mediated activation after latency is established. These findings may explain why, despite the expression of HIF-1α in Kaposi’s sarcoma tumors, KSHV remains in latency, because HIF-1α cannot induce lytic genes once the viral DNA is heterochromatinized. Importantly, we also demonstrate that inhibition of the epigenetic repressor PRC2, which associates with lytic promoters after 24 hpi, restores HIF-1α’s ability to bind viral promoters and induce lytic gene expression post-latency. Collectively, our results indicate that not only the presence of HIF-1α, but also the timing and duration of its expression during KSHV infection, are critical determinants of its ability to drive lytic infection. IMPORTANCE The current view is that the default pathway of KSHV infection is the establishment of latency, however, how this is altered under physiological stress conditions remains largely unknown. We previously showed that hypoxia, or the expression of its transcription factor HIF-1α alone, promotes the establishment of lytic rather than latent KSHV infection. In this study, we show that the duration of hypoxia, as well as the timing and duration of HIF-1α expression, are crucial determinants in facilitating lytic de novo KSHV infection. Notably, we found that PRC2-mediated heterochromatin inhibits the HIF-1α-mediated upregulation of lytic genes as chromatinization of the KSHV genome progresses during infection. Our findings offer a deeper understanding of how epigenetic regulation intersects with host stress responses to influence viral pathogenesis.

  PublisherDOI

• Long-read transcriptomics of caviid gammaherpesvirus 1: compiling a comprehensive RNA atlas

  mSystems · 2025-02-27 · 4 citations

  articleOpen access

  Caviid gammaherpesvirus 1 (CaGHV-1), formerly known as the guinea pig herpes-like virus, is an oncogenic gammaherpesvirus with a sequenced genome but an as-yet uncharacterized transcriptome. Using nanopore long-read RNA sequencing, we annotated the CaGHV-1 genome and constructed a detailed transcriptomic atlas. Our findings reveal diverse viral mRNAs and non-coding RNAs, along with mapped promoter elements for each viral gene. We demonstrated that the CaGHV-1 RTA lytic cycle transcription factor activates its own promoter, similar to Kaposi's sarcoma-associated herpesvirus (KSHV), and that the CaGHV-1 ORF50 promoter responds to RTA proteins from other gammaherpesviruses, highlighting the evolutionary conservation of RTA-mediated transcriptional mechanisms. Additionally, our analysis uncovered extensive transcriptional overlap within the viral genome, suggesting a role in regulating global gene expression. Given its tumorigenic properties, broad host range, and non-human pathogenicity, this work establishes CaGHV-1 as a promising small animal model for investigating human gammaherpesvirus pathogenesis. IMPORTANCE: The molecular underpinnings of gammaherpesvirus pathogenesis remain poorly understood, partly due to limited animal models. This study provides the first comprehensive transcriptomic atlas of CaGHV-1, highlighting both coding and non-coding RNAs and revealing regulatory elements that drive viral gene expression. Functional studies of the CaGHV-1 RTA transcription factor demonstrated its ability to self-activate and cross-activate promoters from homologous gammaherpesviruses, reflecting conserved mechanisms of transcriptional control. These findings solidify CaGHV-1 as a unique and versatile small animal model, offering new opportunities to investigate gammaherpesvirus replication, transcriptional regulation, and tumorigenesis in a controlled experimental system.

  PublisherDOI

• Virology—the path forward

  Journal of Virology · 2024-01-03 · 9 citations

  articleOpen access

  In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avoid impeding science that is essential for rapidly reducing and responding to pandemic threats as well as addressing more common challenges caused by infectious diseases. Decades of research uniquely positioned the US to be able to respond to the COVID-19 crisis with astounding speed, delivering life-saving vaccines within a year of identifying the virus. We should embolden and empower this strength, which is a vital part of protecting the health, economy, and security of US citizens. Herein, we offer our perspectives on priorities for revised rules governing virology research in the US.

  PublisherOA PDFDOI

• Genome-Wide Transcriptional Roles of KSHV Viral Interferon Regulatory Factors in Oral Epithelial Cells

  Viruses · 2024-05-25

  articleOpen accessCorresponding

  The viral interferon regulatory factors (vIRFs) of KSHV are known to dysregulate cell signaling pathways to promote viral oncogenesis and to block antiviral immune responses to facilitate infection. However, it remains unknown to what extent each vIRF plays a role in gene regulation. To address this, we performed a comparative analysis of the protein structures and gene regulation of the four vIRFs. Our structure prediction analysis revealed that despite their low amino acid sequence similarity, vIRFs exhibit high structural homology in both their DNA-binding domain (DBD) and IRF association domain. However, despite this shared structural homology, we demonstrate that each vIRF regulates a distinct set of KSHV gene promoters and human genes in epithelial cells. We also found that the DBD of vIRF1 is essential in regulating the expression of its target genes. We propose that the structurally similar vIRFs evolved to possess specialized transcriptional functions to regulate specific genes.

  PublisherOA PDFDOI

• KSHV 3.0: a state-of-the-art annotation of the Kaposi’s sarcoma-associated herpesvirus transcriptome using cross-platform sequencing

  mSystems · 2024-01-11 · 17 citations

  articleOpen access

  Kaposi's sarcoma-associated herpesvirus (KSHV) is a large, oncogenic DNA virus belonging to the gammaherpesvirus subfamily. KSHV has been extensively studied with various high-throughput RNA-sequencing approaches to map the transcription start and end sites, the splice junctions, and the translation initiation sites. Despite these efforts, the comprehensive annotation of the viral transcriptome remains incomplete. In the present study, we generated a long-read sequencing data set of the lytic and latent KSHV transcriptome using native RNA and direct cDNA-sequencing methods. This was supplemented with Cap Analysis of Gene Expression sequencing based on a short-read platform. We also utilized data sets from previous publications for our analysis. As a result of this combined approach, we have identified a number of novel viral transcripts and RNA isoforms and have either corroborated or improved the annotation of previously identified viral RNA molecules, thereby notably enhancing our comprehension of the transcriptomic architecture of the KSHV genome. We also evaluated the coding capability of transcripts previously thought to be non-coding by integrating our data on the viral transcripts with translatomic information from other publications.IMPORTANCEDeciphering the viral transcriptome of Kaposi's sarcoma-associated herpesvirus is of great importance because we can gain insight into the molecular mechanism of viral replication and pathogenesis, which can help develop potential targets for antiviral interventions. Specifically, the identification of substantial transcriptional overlaps by this work suggests the existence of a genome-wide interference between transcriptional machineries. This finding indicates the presence of a novel regulatory layer, potentially controlling the expression of viral genes.

  PublisherDOI

• Long-read Transcriptomics of Caviid Gammaherpesvirus 1: Compiling a Comprehensive RNA Atlas

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-12-14

  preprintOpen access

  ABSTRACT Caviid gammaherpesvirus 1 (CaGHV-1), formerly known as the guinea pig herpes-like virus, is an oncogenic gammaherpesvirus with a sequenced genome but an as-yet uncharacterized transcriptome. Using nanopore long-read RNA sequencing, we annotated the CaGHV-1 genome and constructed a detailed transcriptomic atlas. Our findings reveal diverse viral mRNAs and non-coding RNAs, along with mapped promoter elements for each viral gene. We demonstrated that the CaGHV-1 RTA lytic cycle transcription factor activates its own promoter, similar to KSHV, and that the CaGHV-1 ORF50 promoter responds to RTA proteins from other gammaherpesviruses, highlighting the evolutionary conservation of RTA-mediated transcriptional mechanisms. Additionally, our analysis uncovered extensive transcriptional overlap within the viral genome, suggesting a role in regulating global gene expression. Given its tumorigenic properties, broad host range, and non-human pathogenicity, this work establishes CaGHV-1 as a promising small animal model for investigating human gammaherpesvirus pathogenesis. IMPORTANCE The molecular underpinnings of gammaherpesvirus pathogenesis remain poorly understood, partly due to limited animal models. This study provides the first comprehensive transcriptomic atlas of CaGHV-1, highlighting both coding and non-coding RNAs and revealing regulatory elements that drive viral gene expression. Functional studies of the CaGHV-1 RTA transcription factor demonstrated its ability to self-activate and cross-activate promoters from homologous gammaherpesviruses, reflecting conserved mechanisms of transcriptional control. These findings solidify CaGHV-1 as a unique and versatile small animal model, offering new opportunities to investigate gammaherpesvirus replication, transcriptional regulation, and tumorigenesis in a controlled experimental system.

  PublisherOA PDFDOI

• Correction for Rasmussen et al., “Virology—the path forward”

  Journal of Virology · 2024-02-09 · 4 citations

  erratumOpen access

  7: "elevating SARS-CoV-1 to a select agent in 2009" should read "elevating SARS-CoV-1 to a select agent in 2012."The CDC proposed adding SARS-CoV-1 to the Select Agent registry in a federal notice on 13 July 2009 (https://www.federalregister.gov/documents/2009/07/13/E9-16536/posses sion-use-and-transfer-of-select-agents-and-toxins-proposed-addition-of-sars-associ ated).This notice of proposed rulemaking explicitly states that compliance with the proposed amendment would require anyone possessing SARS-CoV-1 to obtain current or amended registration with the HHS Select Agent Program and acknowledged that registration is a time-consuming and potentially costly process.Contemporaneous sources demonstrate that the research impact was anticipated in 2009 (https://absa.org/wpcontent/uploads/2017/01/090911DHHS_SARS_Select_Agent_Comments.pdf and https:// www.cidrap.umn.edu/sars/cdc-proposes-list-sars-virus-select-agent) and had already had a negative impact on SARS-CoV-1 research (S.

  PublisherOA PDFDOI

• Novel Herpesvirus Transcripts with Putative Regulatory Roles in DNA Replication and Global Transcription

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-03-27

  preprintOpen access

  ABSTRACT In the last couple of years, the rapid advances and decreasing costs of sequencing technologies have revolutionized transcriptomic research. Long-read sequencing (LRS) techniques are able to detect full-length RNA molecules in a single run without the need for additional assembly steps. LRS studies have revealed an unexpected transcriptomic complexity in a variety of organisms, including viruses. A number of transcripts with proven or putative regulatory role, mapping close to or overlapping the replication origins (Oris) and the nearby transcription activator genes, have been described in herpesviruses. In this study, we applied both newly generated and previously published LRS and short-read sequencing datasets to discover additional Ori-proximal transcripts in nine herpesviruses belonging to all of the three subfamilies (alpha, beta and gamma). We identified novel long non-coding RNAs (lncRNAs), as well as splice and length isoforms of mRNAs and lncRNAs. Furthermore, our analysis disclosed an intricate meshwork of transcriptional overlaps at the examined genomic regions. Our results suggest the existence of a ‘super regulatory center’, which controls both the replication and the global transcription through multilevel interactions between the molecular machineries.

  PublisherOA PDFDOI

• KSHV RTA utilizes the host E3 ubiquitin ligase complex RNF20/40 to drive lytic reactivation

  Journal of Virology · 2023-10-27 · 10 citations

  articleOpen accessSenior author

  ABSTRACT Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic DNA virus whose lytic replication cycle is induced and driven by the viral transcription factor RTA (replication and transcription activator). Identifying what cellular and viral proteins RTA is interacting with during lytic reactivation can help to better understand how RTA promotes the lytic cycle. Using a proteomic approach, we identified the cellular E3 ubiquitin ligase complex RNF20/40 as a novel interacting partner of RTA. One of the major roles of this protein complex is the monoubiquitylation of histone H2B at lysine 120 on cellular chromatin, which is a hallmark of transcriptionally active genes. While the role of RNF20/40 has been studied on different host genomes, its potential to regulate viral genes remains largely unexplored. Here, we show that the shRNA inhibition of RNF20 expression impairs RTA-induced host and viral lytic gene expression, viral DNA replication, and virus production. In addition, we found that the association of RNF20 with the KSHV episome increases during lytic reactivation, and the binding of RTA to viral promoters is required for the synergistic promoter activation by RTA and RNF20/40. Interestingly, the inhibition of RNF20 expression during lytic reactivation of KSHV did not affect H2BK120ub level but it did reduce RNA polymerase II occupancy on viral promoters. Overall, our data suggest that RTA is hijacking the cellular E3 ligase complex RNF20/40 to increase the level of transcriptionally active RNA polymerase II on viral gene promoters thereby facilitating lytic gene expression to advance the viral lytic cycle. IMPORTANCE Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-causing human herpesvirus that establishes a persistent infection in humans. The lytic viral cycle plays a crucial part in lifelong infection as it is involved in the viral dissemination. The master regulator of the KSHV lytic replication cycle is the viral replication and transcription activator (RTA) protein, which is necessary and sufficient to push the virus from latency into the lytic phase. Thus, the identification of host factors utilized by RTA for controlling the lytic cycle can help to find novel targets that could be used for the development of antiviral therapies against KSHV. Using a proteomics approach, we have identified a novel interaction between RTA and the cellular E3 ubiquitin ligase complex RNF20/40, which we have shown to be necessary for promoting RTA-induced KSHV lytic cycle.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R03DE025562

  NIH · $236k · 2018

• NIH Grant R21AI119597

  NIH · $431k · 2018

• Viral and host strategies for regulation of KSHV infection

  NIH · $1.9M · 2018–2024

• Immune evasion mechanisms by a tumor herpesvirus in the oral cavity

  NIH · $1.8M · 2020–2026

Frequent coauthors

• Bernadett Papp

  University of Florida

  140 shared

• Juan D. Alonso

  University of Florida

  36 shared

• Nenavath Gopal Naik

  University of Florida

  35 shared

• Lauren McKenzie Spires

  Florida College

  32 shared

• See-Chi Lee

  Florida College

  31 shared

• Seung Jin Jang

  University of Florida

  24 shared

• Jae U. Jung

  Cleveland Clinic Lerner College of Medicine

  23 shared

• Natalie Atyeo

  University of Florida

  20 shared

Awards & honors

• 2026 UFRF Professor