Primary Appointment:
 Department of Medicine

GEBS Cluster Affiliations:
 Immunology, Microbiology, and Virology - IMV

University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 689
Rochester, New York 14642

Phone: (585) 275-5871
E-Mail: william_bonnez@urmc.rochester.edu

Experimental Human Papillomavirus Infections

My main area of research concerns genital human papillomaviruses (HPV). Different HPV genotypes cause different diseases. For example, HPV-6 and HPV-11 are responsible for most external genital warts and many benign lesions of the uterine cervix. In contrast, HPV-16, -18, and related HPVs cause incipient (dysplasias or intraepithelial neoplasias) and invasive cancers of the uterine cervix, the anus, and of other genital sites. The inability so far to propagate HPVs in vitro remains a considerable barrier to research on these viruses. Our work relies largely on human xenograft implanted in immunodeficient mice that allow us to grow and propagate HPVs (6, 11, 16), and faithfully recapitulate the clinical, histologic, and molecular features of the naturally occurring human lesions (warts and dysplasias).

1. We are using these animal models for two related purposes:
   
   • Evaluation of antiviral agents - This activity is part of an NIH contract to offer the drug industry and independent investigators a mean to identify potential antiviral agents.
     
     
   • Study of the pathogenicity of HPV infections - We can now compare the molecular pathogenesis, over time and across different tissue, of the actual lesions caused by of low-risk oncogenic HPV-6 and high-risk oncogenic HPV-16.
     
2. We are also developing an in vitro model, based on an artificial skin, to increase the versatility of our methods, and to propagate HPV from either virions or viral DNA. These tools should permit to better establish the exact role of some of the more than 220 HPV genotypes in the pathogenesis of some cancers.
   
   

Bonnez W. The 19th International Papillomavirus Conference. Antivir Ther. 7:67-72, 2002.

Bonnez W. Chap. 27 - Papillomavirus. In Clinical Virology. Douglas D. Richman, Richard J. Whitley, and Frederick G. Hayden (editors). 2nd edition. American Society for Microbiology, Washington, NY. 2002. In Press.

Evans TG, Bonnez W, Rose RC, Koenig S, Demeter L, Suzich JA, O'Brien D, Campbell M, White WI, Balsley J, Reichman RC. A Phase 1 Study of a Recombinant Viruslike Particle Vaccine against Human Papillomavirus Type 11 in Healthy Adult Volunteers. J Infect Dis. 183:1485-1493, 2001.

Bonnez W, DaRin C, Borkhuis C, de Mesy Jensen K, Reichman RC, Rose RC. Isolation and propagation of human papillomavirus type 16 in human xenografts implanted in the severe combined immunodeficiency mouse. J Virol 72:5256-61, 1998.

White WI, Wilson SD, Bonnez W, Rose RC, Koenig S, Suzich JA. In vitro infection and type-restricted antibody-mediated neutralization of authentic human papillomavirus type 16. J Virol 72:959-64, 1998.

Bonnez W, Oakes D, Bailey-Farchione A, Choi A, Hallahan D, Corey L, Barnum G, Pappas PG, Halloway M, Stoler MH, Reichman RC. A randomized, double-blind trial of parenteral low dose versus high dose interferon-beta in combination with cryotherapy for treatment of condyloma acuminatum. Antiviral Res 35:41-52, 1997.