Qiyi Tang

Associate Professor

Department of Microbiology


Research Info

Research Support
  1. Epigenetic studies of Kaposi’s Sarcoma-associated Herpesvirus (KSHV).
    PI: Qiyi Tang
    Agency: NIH/NCRR
    Grant Number U54RR022762, $50,000
    Period: 09/01/2010 to 08/31/2011
    This proposal aims to elucidate the mechanisms of KSHV reactivation.

  2. MIE gene splicing is a new target for HCMV Caused Disease
    PI: Qiyi Tang
    Agency: NIH/NCRR,
    pilot grant of RCMI 2G12RR003050 $100,000 per year for 5 years
    Period: 01/01/2009 to 12/31/2013
    This proposal aims to develop anti-sense micro RNA to interfere with HCMV MIE gene splicing to inhibit MIE gene expression and hence viral replication.

  3. Functions of RTA and K8 in KSHV reactivation
    PI: Qiyi Tang
    Agency: American Cancer Society, Research Scholar Grant 117448-RSG-09-289-01-MPC
    Period: 01/01/2010 to 12/31/2013
    This proposal aims to elucidate the functions of K8 and RTA of KSHV.

(1) A functional link between K8 SUMOylation and KSHV reactivation
PI: Qiyi Tang
Grant Number: IRG-92-032-13 $30,000 American Cancer Society subcontract H. Lee Moffitt sub award # 60-14599-01-01-S6
Period: 1/1/2009 – 12/31/2010


Research Interest

My studies have been focused on cellular intrinsic defense against infecting viruses. The cell uses widely different cellular proteins, in its defensive arsenal, such as promyelocytic leukemia (PML) bodies components, nuclear suppressors, apoptotic pathway molecules, and pre-mRNA splicing inhibitors (PTB family proteins). Viruses have also evolved molecular anti-defense mechanisms. For example, cytomegalovirus (CMV) gene products IE2 and Kaposi’s sarcoma herpes virus (KSHV) ORF45 gene products suppresses IFN production, ul36-37 has anti-apoptotic effects, IE1 disperses PML bodies and represses HDAC activity. These studies will advance our understanding of the mechanisms of CMV and KSHV latency and reactivation and may lead to the development of new therapies to prevent CMV- and KSHV-caused disease.

There is a fundamental gap in understanding how the cytomegalovirus (CMV) major-immediate early (MIE) gene is regulated at the splicing level, and how the virus usurps cellular gene-splicing machinery for viral gene splicing. Continued existence of this gap represents an important problem because, until it is filled, the interaction of CMV with host cells at the early stage remains incomprehensible. The MIE gene is essential to the replication of CMV because MIE gene products (such as IE1 and IE2) are essential for CMV early and late gene expression, and HCMV with a deleted MIE gene can only replicate in MIE gene-complemented cells. In addition, understanding the mechanisms CMV uses for MIE gene splicing regulation might aid the development of novel strategies against CMV infection. The long-term goal is to understand how MIE gene splicing can be manipulated by the interaction of CMV with host cells. The objectives in this proposal, which represent our next steps in pursuit of that goal, are to determine how the MIE gene products are regulated at the splicing level and to determine, as well, the biological importance of MIE gene splicing with regard to CMV replication in vitro and in vivo.

B. KSHV PROTEINS POSTTRANSLATIONAL MODIFICATION AND REACTIVATION. I recently received an award (RSG) from the American Cancer Society that will support me in a Kaposi’s sarcoma-associated herpesvirus (KSHV) project for four years. I have always been interested in the roles of K8 and RTA (replication and transcription activator) proteins on viral reactivation, especially in the epigenetic modifications of the two proteins. Various new technologies will be employed for the project including KSHV DNA BAC techniques, epigenetic analysis and construction of KSHV latency.

KSHV (also known as Human herpesvirus 8) has been determined to be the most frequent cause of malignancies in AIDS patients. It is associated primarily with Kaposi’s sarcoma and primary effusion lymphoma (PEL), as well as with multicentric Castleman’s disease (MCD). The switch from the latent to the lytic stage is important both in maintenance of malignancy and viral infection. Therefore, strategies for the treatment of KSHV-related malignancies need to both prevent cellular proliferation and block viral production. Only a few genes can be expressed during latency, and these gene products tether KSHV DNA episomes with chromosomes in order to keep KSHV in its latent state. Several chemicals, including 12-O-Tetradecanoyl-phorbol-13-acetate (TPA), sodium butyrate (NaB), and 5-azacytidine (5-AC), can reactivate KSHV from latency in cell cultures. RTA (also called ORF50) gene expression is the switch point from latency to the lytic cycle because RTA is essential and sufficient for the reactivation of KSHV, but the pathological mechanism of the reactivation of KSHV is poorly understood. Prior studies on the reactivation of KSHV using chemical inducers implied that epigenetic modification, especially chromatin remodeling by acetylation, is critical for transactivators to access lytic gene promoters.

The studies in this proposal emphasize that the reactivation of KSHV is critical to its pathogenesis and especially so to tumorigenesis. By studying the two essential genes, RTA and K8, we expect to develop a clearer understanding of the importance of two different factors on KSHV reactivation: the epigenetic modulation (acetylation and deacetylation) of RTA and the interaction of HDAC with K8. We also expect to provide information through this approach for anti-KSHV-caused tumor therapy. These studies will contribute to our understanding of the mechanism of how KSHV can be reactivated

C. CYTOMEGALOVIRUS-host interaction in Human cytomegalovirus (HCMV) infection causes life-threatening diseases in immunocompromised hosts, thus representing a large worldwide population. HCMV can infect all types of organs and tissues and therefore causes a broad range of diseases, including CNS abnormalities, pneumonia, hepatitis and gastrointestinal problems. How to explain the protean manifestations of HCMV infection has been a challenge for decades. Cell culture is a powerful tool to analyze whether a given cell type is able to support virus entry, gene expression, virus production and release, and for identification of viral genes with apparent cell type specific activity. Unfortunately the information obtained from cell culture experiments cannot be simply transferred to the host situation or patient. Furthermore, the in vitro milieu can alter cell physiology, which might transform cellular properties with respect to virus infection. Therefore, the virus-cell interactions in CMV infection should be studied in the physiological environment of the intact host organism, namely an animal model. Human CMV (HCMV) only infects humans, and to date the infection of mice with murine CMV (MCMV) is the most informative small animal model for HCMV infection. Therefore, more detailed studies of the pathogenesis for different cell and tissue types during MCMV infection in mouse models are crucial.

Our long-term goal is to understand the interactions of virus-host in specific organs and tissues and to determine how CMV infection can cause adaptively variant damage to different tissues. Our objective is to set up a mouse model for tissue-specific infection of cytomegalovirus so that we can investigate viral pathogenesis in both a spatial and temporal manner.

Conditional or inducible Cre-transgenic mice have been available commercially for several years. These mice provide a convenient resource for studying viral infections in tissue- or cell-specific manner. In our laboratory, we have routinely used the BAC system to make mutations of large DNA viruses. We will combine the BAC mutagenesis techniques and Cre/lox system to localize CMV infection in the tissues of our interest. By studying tissue-specific infection of CMV, we will instigate a new field in viral pathology.