4), leading to constitutive expression of E6 and E7 proteins in HPV-associated cancers. The continuous expression of these two viral oncoproteins contributes to the maintenance of proliferation and malignant phenotypes of the cancer check details cells due to their disruptive action on cell cycle

checkpoint. Therefore, E6 and E7 are considered to be potential therapeutic targets for blocking the development of HPV-related cancer. Ideally, small molecules that target and prevent the interaction of E6 and E7 with cellular proteins may have interesting antiproliferative potential (Manzo-Merino et al., 2013). Besides E6 and E7, part or all of E1 is transcribed and translated in neoplasias. The amino-terminal portion of E1 protein or a truncated peptide is essential to bind to and neutralize over-abundant cyclins that are transcriptionally up-regulated by E7 (Stoler et al., 1992, Lin et al., 2000 and Coupe et al., 2012). The name polyomavirus is derived from the ability of the first PyV discovered more than 50 years ago to induce multiple (poly) tumors (oma) in mice. However, most PyVs do not cause tumors in their natural host. Mouse polyomavirus (MPyVs) and the simian vacuolating agent 40 (SV40) were the first PyVs identified (Atkin et al., 2009). Two human PyVs were identified in 1971 and were named following the patients’ initials from whom they were isolated [JC polyomaviruses (JCPyV)

was identified in a brain tissue extract from a patient (John Cunningham) with progressive multifocal leukoencephalopathy (PML) and BK polyomavirus (BKPyV) was isolated from the urine of a nephropathic kidney LY2109761 in vivo transplant patient of unknown name] (Dalianis and Hirsch, 2013, Hirsch et al., 2013 and Gjoerup and Chang, 2010). Subsequently, more PyVs Protirelin were identified in mammals and birds. From 2007 on, several

new human PyVs have been discovered, including KI (Karolinska Institutet) virus (KIPyV), WU (Washington University) virus (WUPyV), Merkel cell polyomavirus (MCPyV), HPyV6, HPyV7, HPyV9, Trichodysplasia spinulosa virus (TSPyV), HPyV10 [Malawi virus (MWPyV and MX polyomavirus (MXPyV) variants], HPyV12 and Saint Louis Polyomavirus (STLpYV) ( Van Ghelue et al., 2012, Pastrana et al., 2013, Ehlers and Wieland, 2013, Yu et al., 2012, Feltkamp et al., 2013 and White et al., 2013). Serological studies indicate that human PyVs sub-clinically infect the general population with rates ranging from 35% to 90%, and significant disease is only observed in patients with impaired immune functions (Dalianis and Hirsch, 2013 and Chang and Moore, 2012). Thus, BKPyV has been linked to hemorrhagic cystitis (HC) after allogenic hematopoietic stem cell transplantation and PyV-associated nephropathy (PyVAN) after kidney transplantation, while JCPyV is associated with PML in HIV-AIDS, haematological diseases and in autoimmune diseases treated with certain lymphocyte-specific antibodies (Dalianis and Hirsch, 2013, Bennett et al., 2012 and Jiang et al., 2009). TSPyV was identified in T.