An inhibitor of the epidermal growth factor receptor function does not affect the ability of human papillomavirus 11 to form warts in the xenografted immunodeficient mouse model

• Published in: Antiviral research 2007-04, Vol.74 (1), p.43-50
• Main Authors: Parkinson, Tanya, Howett, Mary K., Welsh, Patricia A., Patrick, Susan D., Neely, Elizabeth B., Flanagan, Neil, Pollack, Vincent A., Pustilnik, Leslie R., Moyer, Jim, Perros, Manos
• Format: Article
• Language: English
• Subjects: Administration, Oral; Administration, Topical; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Disease Models, Animal; EGFR; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Epidermal growth factor; Female; HPV; Human papillomavirus; Human papillomavirus 11; Human papillomavirus 11 - physiology; Human viral diseases; Humans; Immunocompromised Host - drug effects; Infectious diseases; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Papillomavirus; Pharmacology. Drug treatments; Quinazolines - administration & dosage; Quinazolines - chemistry; Quinazolines - pharmacology; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - physiology; Transplantation, Heterologous; Tumor Virus Infections - virology; Viral diseases; Viral diseases with cutaneous or mucosal lesions and viral diseases of the eye; Virus Replication - drug effects; Warts - virology
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2006.12.004

Epidermal growth factor receptor (EGFr) has been shown to be induced and activated in cells infected with HPV, suggesting that it may play a physiological role in viral replication or in the formation or maintenance of warts. To investigate this possibility, human foreskin tissue was infected with HPV11 and transplanted onto the renal capsule and the dermis of immunodeficient mice. The animals were treated orally or topically with the potent EGFr inhibitor CP-545130, with treatment starting either immediately following graft attachment, or following a 70 day period to allow development of warts. The rate of appearance of warts, wart size and number were monitored. In addition, we measured intra-lesional HPV replication levels and examined the morphology of the graft tissues. Analysis of the results showed no significant difference between placebo and compound-treated groups, despite high levels of compound present in the graft tissue. We conclude that EGFr kinase activity is not required for the development and maintenance of HPV-11-induced warts in this model.