Research Interests

My research is focused on DNA replication and maintenance of particular Human papillomaviruses (HPVs) which infect the stratified epithelium of the genital tract. There are currently 20 million Americans infected with genital HPVs with 5.5 million new infections reported each year. While all genital HPVs possess the ability to induce benign warts, the "high-risk" HPVs (Types 16, 18, and 31 for example) are associated with an increased likelihood for progression of lesions to malignant cancer.

In their normal life cycle, HPVs exist as low-copy nuclear plasmids in the host basal epithelium where they can be maintained indefinitely. The viral life cycle is tightly linked to the differentiation program of the stratified epithelium, such that viral genome amplification only occurs in differentiated cells. Viral trans-acting factors, E1 and E2, play an important role in replication; E1, a helicase, recruits polymerase alpha to the origin of replication, while E2 acts cooperatively by binding and recruiting E1 to the origin of replication. E2 functions in two other important ways; by inducing transcription of viral genes, and by improving the inheritance of newly synthesized viral genomes to daughter cells. It is thought that E2 performs this function by tethering viral genomes to mitotic chromosomes, thus allowing accurate partitioning.

The goals of my research are: (1) To investigate the role of E2 in long-term replication of HPV genomes. (2) To determine the contribution of cis-acting elements, independent of viral E1 and E2 proteins, in stable replication of HPV genomes. (3) To identify cellular components which contribute to stable HPV replication.

In order to approach these studies we are using a novel system which allows episomal replication of full-length HPV genomes in yeast (Saccharomyces cerevisiae) (Angeletti et al. 2002). This is a powerful approach since it allows modeling of several HPV functions, including replication, transcription, and encapsidation. The yeast/HPV system provides a convenient means to assess the cis and trans-acting functions required for replication HPVs, as well as superior yeast genetic tools to determine the involvement of cellular genes in these functions.

Another line of investigation will involve analysis of the molecular mechanisms which lead to integration of HPV genomes into host chromosomes. HPV-associated cancers often occur 10-20 years after an initial infection and are usually preceded by a loss of episomal replication followed by integration of the HPV genome. We seek to understand what molecular events occur that give rise to integration of HPV genomes.

Recent Publications

• Rogers, A., Loggen, M., Lee, K. and Angeletti P. C. Multiple Human papillomaviruses can replicate extrachromosomally in Saccaromyces cerevisiae, but Bovine papillomavirus cannot (Submitted)
• Dake, B.T. and Angeletti, P. C.  Cis-elements influence Human papillomavirus encapsidation.  (Submitted).
• Li, J., Wang, X., Liu, J., Wang, H, Tang, W., Sun, Y., Qi, M., Zhou, Y., Angeletti, P. C., Zhao K., and  Zhao, W.  Human Papillomavirus type 58 can replicate and transcribe its early and late genes in Saccharomyces cerevisiae (Submitted)
• Pittyakhajonwut, D. and Angeletti, P. C.  Analysis of cis-elements that facilitate extrachromasol persistence of human papillomaviruses. Virology, Feb 13th (2008).
• Angeletti, P. C., Zhang, L., and Wood C. The Viral Etiology of HIV-associated Malignancies. HIV-1: Molecular Biology and Pathogenesis. Editor: Kuan-Teh Jeang, Elsevier. 56:509-557. (2007).
• Ng’andwe C., Lowe J. J., Richards, P. J., Hause, L. L., Wood, C. and Angeletti, P. C. The distribution of sexually transmitted human papillomaviruses among HIV positive and negative populations in Zambia, Africa. BMC Infectious Diseases. July 16:7(1):77 (2007).
• Ng’andwe C., Lowe J. J., Richards, P. J., Hause, L. L., Wood, C. and Angeletti, P. C. The distribution of sexually transmitted human papillomaviruses among HIV positive and negative populations in Zambia, Africa. BMC Infectious Diseases. July 16:7(1):77 (2007).
• Vaeteewoottacharn, K., Chamutpong, S., Ponglikitmongkol, M. and Angeletti, P. C. Differential localization of HPV16 E6 splice products with E6-associated protein. Virology Journal 2:50 247-260 (2005).
• Angeletti, P. C. Replication and encapsidation of papillomaviruses in Saccharomyces cerevisiae. Human Papillomaviruses: Methods and Protocols, Methods in Molecular Medicine. Editor Doorbar, J., Humana Press, Totowa, NJ. Vol. 50 (2005).
• Kim, K., Angeletti, P. C., Hassebroek, E. C. and Lambert, P. F. Identification of cis-acting elements that mediate the replication and maintenance of human papillomavirus type 16 genomes in Saccharomyces cerevisiae. Journal of Virology 79, 5933-5942 (2005).
• Joung, I., Angeletti P. C. and Engler, J. A.  Functional implications in apoptosis by interferon inducible gene product 1-8D, the binding protein to adenovirus preterminal protein The Journal of Microbiology, 41, 295-299. (2003). 
• Angeletti, P. C., Kim, K., Fernandes, F. J. and Lambert, P. F. Stable replication of papillomavirus genomes in Saccharomyces cerevisiae. Journal of Virology 76, 3350-3358 (2002).
• Angeletti, P. C., Walker, D., and Panganiban, A. T. Small glutamine-rich protein/Viral protein U-binding protein is a novel co-chaperone that affects Hsp70 activity. Cell Stress and Chaperones 7, 258-268 (2002).
• Angeletti, P. C. Replication and encapsidation of papillomaviruses in Saccharomyces cerevisiae. Human Papillomaviruses: Methods and Protocols, Methods in Molecular Medicine. Editor Doorbar, J., Humana Press, Totowa , NJ . (in press).
• Kim, K., Angeletti, P. C., Hassebroek, E. C. and Lambert, P. F. Mapping of cis-acting replication and maintenance signals of HPV16 in Saccharomyces cerevisiae. Journal of Virology 79, 5933-5942 (2005).
• Joung, I. , Angeletti P. C. and Engler, J. A. Functional implications in apoptosis by interferon inducible gene product 1-8D, the binding protein to adenovirus preterminal protein The Journal of Microbiology, 41, 295-299. (2003).
• Angeletti, P. C., Kim, K., Fernandes, F. J. and Lambert, P. F. Stable replication of papillomavirus genomes in Saccharomyces cerevisiae. Journal of Virology 76, 3350-3358 (2002).
• Angeletti, P. C., Walker, D., and Panganiban, A. T. Small glutamine-rich protein/Viral protein U-binding protein is a novel co-chaperone that affects Hsp70 activity. Cell Stress and Chaperones 7, 258-268 (2002).
• Angeletti, P. C. and Engler, J. A. Adenovirus preterminal protein binds to the CAD enzyme at active sites of viral replication on the nuclear matrix. Journal of Virology 72, 2896-2904 (1998).
• Sanchez, V., Angeletti, P. C., Engler, J. A., and Britt, W. J. Localization of human cytomegalovirus structural proteins to the nuclear matrix of infected human fibroblasts. Journal of Virology 72, 3321-3329 (1998).
• Angeletti, P. C., and Engler, J. A. Tyrosine kinase-dependent release of an denovirus reterminal protein complex from the nuclear matrix. Journal of Virology 70, 3060-3067 (1996).
• Lucher, L. A., Kuntirat, B., Chowrira, B., Zhao, J., and Angeletti, P. C. Altered synthesis of adenovirus 12 DNA-binding protein but not DNA polymerase during abortive infection of hamster cells. Virology 189, 187-195 (1992).