Research interest(s)/area of expertise
- With limited genetic materials, viruses are able to overcome multiple layers of host defenses and subjugate the host during infection. Understanding how viruses employ multifunctional viral proteins to target different cell machineries is the primary interest of my research. My lab focuses on herpes simplex virus 1 (HSV-1), a neurotropic virus that establishes lifelong latency in trigeminal ganglion. Sporadically it reactivates and causes a wide range of mild to severe herpetic diseases, which is a major health concern in immunocompromised patients. Due to its unique life cycle, HSV-1 closely interacts with all levels of host immune responses. Upon infection, the incoming viral DNA encounters numerous cell intrinsic anti-viral defenses. Our current project involves an immediate early protein of HSV-1 called ICP0, a multifunctional viral protein that antagonizes multiple host anti-viral mechanisms. On one hand, ICP0 contains an E3 ubiquitin ligase activity which directly targets cellular restrictive factors, such as PML, Sp100, IFI16, for proteasome-dependent degradation. On the other hand, ICP0 interacts with various cellular proteins, including USP7, CoREST, Cyclin D3 and RNF8, to regulate a diverse array of cellular regulatory pathways. Our interest is to understand the molecular basis of how ICP0 coordinates its multiple functions to simultaneously counteract against different anti-viral defense mechanisms. We focus on a nuclear dynamic structure termed nuclear domain 10 (ND10), which contains over 150 regulatory proteins and plays a critical role in restricting viral expression at early HSV-1 infection. Specifically, ICP0 functions to degrade the ND10 organizer, PML, which consequently leads to the dispersal of ND10 and the alleviation of gene repression imposed by ND10. We found that ICP0 achieves this counteraction via a carefully orchestrated stepwise interaction with the ND10 nuclear bodies.
- Ph.D., Ohio State University, Department of Molecular Cellular Biochemistry, 2001
- Post-Doc., University of Chicago, Department of Microbiology, 2011
Awards and grants
R01AI18992 (PI: Haidong Gu)
Title: Dissecting the Functional Domains of Infected Cell Protein 0 of Herpes Simplex Virus 1.
Funding Agency: NIH, National Institute of Allergy and Infectious Diseases
Funding Period: 4/15/2015 – 3/31/2020
Total Cost: $1,882,693
1) Zheng Y, Samrat SK, Gu H*. A tale of two PMLs: elements regulating the differential substrate recognition by the HSV-1 ICP0 E3 ubiquitin ligase. J. Virol. 90 (23): 10875-10885 (2016).
2) Gu H*, Zheng Y. Role of ND10 nuclear bodies in the chromatin repression of HSV-1. Virol J. 13:62. DOI 10.1186/s12985-016-0516-4. (2016). Review.
3) Gu H*. Infected cell protein 0 functional domains and their coordination in herpes simplex virus replication. World J Virol. 5(1):1-13. (2016). Review.
4) Zheng Y, Gu H*. Identification of Three Redundant Segments Responsible for Herpes Simplex Virus 1 Infected Cell Protein 0 to Fuse with ND10 Nuclear Bodies. J. Virol. 89(8):4214-26 (2015).
5) Gu H*, Zheng Y, Roizman B. The interaction of herpes simplex virus ICP0 with ND10 bodies: A sequential process of adhesion, fusion and retention. J. Virol. 87 (18): 10244-10254 (2013).
6) Zerboni L, Che X, Reichelt M, Qiao Y, Gu H, Arvin A*. Herpes simplex virus 1 tropism for human sensory ganglion neurons in the severe combined immunodeficiency mouse model of Neuropathogenesis. J. Virol. 87(5): 2791-2802. (2013).
7) Kalamvoki M, Gu H, Roizman B*. Overexpression of the ubiquitin-specific protease 7 resulting from transfection or mutations in the ICP0 binding site accelerates rather than depresses herpes simplex virus 1 gene expression. J. Virol. 86 (23): 12871-8. (2012).
For a complete list of publications, go to the following URL: http://www.ncbi.nlm.nih.gov/sites/myncbi/haidong.gu.1/bibliography/48244807/public/?sort=date&direction=ascending
Bio 2200 – Introductory Microbiology
Bio 5020/7020 – Comprehensive Virology
Bio 6010 – Molecular Cellular Biology II