Interferon‐Inducible Genes Are Major Targets of Human Papillomavirus Type 31: Insights from Microarray Analysis

Human papillomavirus (HPVs) are small DNA viruses that infect epithelial tissue. More than 70 subtypes of HPV have been identified to date and they exhibit specific tropism to various region of the body [11, 19,33]. Genital HPVs can be divided to high-risk and low-risk groups [19]. The high-risk genital HPVs (HPV16, 18, 31, 33, and 54) are the etiological agents of cervical cancer, whereas low-risk HPVs (HPV6 and 11) are associated with common genital warts. Cervical cancer is the second most common cancer in women world wide, resulting in 500,000 new cases and 200,000 death every year. Because of the lack of the access to routine Pap smears, cervical cancer remains a devastating disease in developing countries [15]. The genome of HPVs encodes only 8 to 10 proteins. The virus must therefore depend on basic cellular machinery to modulate cellular activities in favor of viral replication. As a result, the interaction of viral proteins with the host proteins is essential for viral replication. The best known examples include the interaction of oncoproteins E6 and E7 of high-risk HPVs with p53 and pRB, respectively. These interactions result in degradation and inactivation of p53 by E6 [12,26, 27], and inactivation of pRB by E7, resulting in altered regulation of E2F-inducible genes [5,8,20]. In addition to E6 and E7, HPV E2 protein has been shown to have transactivation/repression activity by binding to specific recognition sequences [3,21], and E5 protein