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Molecular Virology and Microbiology

Houston, Texas

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Department of Molecular Virology and Microbiology
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Paul D. Ling, Ph.D.

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 Paul D. Ling, Ph.D.

Associate Professor
Department of Molecular Virology & Microbiology

Research Interests

Epstein-Barr virus Latency

Currently, our laboratory is focused on two projects:

Project 1: Evasion of intrinsic cellular antiviral defenses by gammaherpesviruses.

Promyelocytic Leukemia Nuclear Bodies (PML NBs) are nuclear organelles organized by the PML protein itself and contain other cellular proteins like Sp100A and Daxx. PML NBs mediate an intrinsic cellular antiviral defense, especially against herpesviruses. Recent work from our laboratory has found that Epstein-Barr virus, a human herpesvirus associated with several B cell malignancies, encodes a protein that interacts with the PML NB-associated protein Sp100A. Our hypothesis is that EBNA-LP counteracts PML NB-mediated repression of viral gene expression through its interactions with Sp100. We are currently using genetic, biochemical, and molecular approaches to understand the mechanisms by which EBNA-LP association with Sp100 mediates efficient B cell immortalization by EBV. These studies will provide valuable insight into the mechanisms of EBV-mediated B cell immortalization, the pathogenesis of EBV-associated malignancies, viral persistence, and possibly B cell biology in general. In addition, we are hopeful that our investigations will reveal what the normal function of Sp100 is, which remains to be clarified.

How PML affects the outcome of herpesvirus infections in vivo remains to be clarified because facile animal models for human herpesvirus infections are lacking. To address this, we recently determined that murine gammaherpesvirus 68 (gHV68) mediates an efficient proteasome dependent degradation of PML and this is important for infection in cell culture. We have determined that this activity is carried out by the viral tegument protein ORF75c and are currently investigating its mechanism of action. gHV68 is emerging as an excellent system for investigating gammaherpesvirus biology in vivo. Our results provide the groundwork for using this system to investigate how PML modulates herpesvirus infections in vivo, which we are currently pursuing.

Project 2: To develop diagnostic tools, treatments, and vaccines for endothelioltropic elephant herpesvirus (EEHV), a highly lethal infection of endangered Asian elephants.

Over the past decade several species of novel herpesviruses have been identified and are now known as Probosciviruses in captive elephants. Nearly 50 cases of rapidly fatal hemorrhagic disease attributed to five of these elephant endotheliotropic herpesviruses have been documented, with the majority affecting young captive-bred Asian elephants. There is no available vaccine for this virus and it remains unclear how susceptible EEHV is to the anti-herpesvirus drug famciclovir, which is currently the drug of choice used for treating primary infection. Our research is focused on answering the following questions:

  • How is EEHV transmitted?
  • Where are the sites of latent and reactivating virus?,
  • Can the EEHV virus be cultivated in the laboratory?
  • Can we develop an EEHV vaccine?

This work is being pursued in collaboration with the Houston Zoo.

News Items

Contact Information

Department of Molecular Virology & Microbiology
Baylor College of Medicine
One Baylor Plaza, MS BCM385
Houston, TX, 77030, U.S.A.

713-798-8474
pling@bcm.edu

Education

Ph.D. - Uniformed Services University of the Health Sciences
Postdoctoral - Johns Hopkins School of Medicine

International Association for Research on Epstein-Barr virus and Associated Diseases

Recent Publications (PubMed)

Ling, P.D., Peng, R.S., Nakajima, A., Yu, J.H., Tan, J., Moses, S.C., Yang, W-H., Zhao, B., Kieff, E., Bloch, K.D., and D.B. Bloch. 2005. Mediation of Epstein-Barr virus EBNA-LP transcriptional coactivation by the PML nuclear body-associated protein Sp100. EMBO J. 24:3565-3575.

Echendu, C.W. and P. D. Ling. 2008. Epstein-Barr virus EBNA-LP function is refractory to the effects of type I interferons. J. Cytokine and Interferon Res. 28: 667-678.

Ling, P. D., Tan, J., Sewatanon, J., and R.S. Peng. 2008. The murine gammaherpesvirus 68 ORF75c tegument protein induces the degradation of PML and is essential for production of infectious virus. J. Virol. 82: 8000-8012.

Ling, P. D. 2009. EBNA-LP Function. In Epstein-Barr virus latency and transformation, E.S. Robertson (ed), Horizon Press. In Press.

Ling, P. D., Tan, J., and R.S. Peng. 2009. Nuclear-cytoplasmic shuttling is not required for EBV EBNA-LP coactivation function. J. Virol. 83:7109-7116.

Students

Jaturong Sewatanon