Herpesviruses and Host Cell Interaction

Our laboratory studies two herpesviruses, human cytomegalovirus (HCMV) and Varicella-Zoster virus (VZV). Our goal is to understand HCMV and VZV pathogenesis - specifically, how these viruses interact with host cells, replicate in and cause diseases.

HCMV infects approximately 80% of the adult population.HCMV is a major cause of infectious morbidity and mortality in immunocompromised individuals, especially in AIDS and transplant patients. HCMV infection also is a leading cause of birth defects.

Since animal models for studying HCMV replication and pathogenesis are not available, severe combined immunodeficient mice implanted with human tissue provide an alternative model for these studies. HCMV clinical isolates replicate to high titers in implanted human tissue; however, attenuated strains have completely lost this ability. The major difference between clinical and attenuated strains is a 15-kb segment encoding 19 viral genes that is present in all virulent strains but absent in attenuated strains. We plan to map the important genes in this region and study their function in viral replication and pathogenesis.

VZV causes chickenpox and shingles. It has a 125-kb genome and encodes 70 unique open reading frames (ORFs). The functions of many its ORFs are not clear. The generation of recombinant VZV has been hindered by its highly cell-associated nature in cultured cells and its poor infectivity of purified VZV DNA. A major advance in VZV genetics was the cloning of the genome as four overlapping segments into cosmids, which significantly improved isolation of mutant strains. However, cosmid systems are difficult to master and making mutants is laborious. For this reason, knowledge about the function of many VZV proteins and their role in pathogenesis lags behind many other herpesviruses. To make these studies more efficient, we have recently cloned a complete VZV genome as a bacterial artificial chromosome. This allows us to stably manipulate and propagate VZV genomic DNA in E. coli. Furthermore, we can efficiently generate recombinant VZV for studies of VZV gene function in different systems.

Selected Publications

• Selariu A, Cheng T, Tang Q, Silver B, Yang L, Liu C, Ye X, Markus A, Goldstein RS, Cruz-Cosme RS, Lin Y, Wen L, Qian H, Han J, Dulal K, Huang Y, Li Y, Xia N and Zhu H: ORF7 of Varicella-Zoster Virus Is a Neurotropic Factor. Journal of virology 86: 8614-24, 2012.

• Warden, C., Q. Tang, H. Zhu. 2010. Herpesvirus BACs: Past, Present, and Future. Journal of Biomedicine and Biotechnology. 2011, 1-16.

• Zhang, Z., Y. Huang, and H. Zhu. 2010. An Efficient Protocol for VZV BAC-Based Mutagenesis. P75-86. In Methods in Molecular Biology, J. Braman (ed.), Humana Press.

• Zhang, Z., A. Selariu, C. Warden, G. Huang, Y. Huang, O. Zaccheus, T. Chen, N. Xia, H. Zhu. 2010. Genome-wide mutagenesis reveals that ORF7 is a novel VZV skin-tropic factor. PLoS Pathogens. 6(7), e1000971.

• Zhang, Z., J. Rowe, W. Wang, M. Sommer, A. Arvin, J. Moffat, H. Zhu. 2007. Genetic Analysis of Varicella Zoster Virus ORF0 to 4 Using A Novel Luciferase Bacterial Artificial Chromosome System. Journal of Virology. 81, 9024-33.

• Netterwald, J., S. Yang, W. Wang, S. Ghanny, M. Cody, P. Soteropoulos, B. Tian, W. Dunn, F. Liu, and H. Zhu. 2005. Two GAS-like elements in the human cytomegalovirus major immediate-early promoter/enhancer are important for viral replication. Journal of Virology. 79, 5935-5046.

• Wang, W., S.L. Taylor, S.A. Leisenfelder, R. Morton, J.F. Moffat, S. Smirnov, and H. Zhu. 2005. Human cytomegalovirus genes in the 15-Kb region are required for viral replication in implanted human tissues in SCID mice. Journal of Virology. 79, 2115-2123.

• Marchini, A., H. Liu, and H. Zhu. 2001. Human cytomegalovirus with IE-2 (UL122) deleted fails to express early lytic genes. Journal of Virology 75, 1870-1878.

Training and Positions

1993 Ph.D. in Biochemistry, Columbia University, NY, NY, mentor: Ron Prywes

1993-1998 Postdoctoral fellow in Virology, Princeton University, NJ, mentor: Thomas Shenk

1998-present Asst. Prof. to Assoc. Prof. (2005), Microbiology & Mol. Genet., Rutgers NJMS (Former UMDNJ-NJMS)