title: Redox control of viral carcinogenesis: The human papillomavirus paradigm.
abstract: BACKGROUND
  Cervical cancer is the second most common neoplastic disease among women worldwide. The initiating event of such cancer is the infection with certain types of human papillomavirus (HPV), a very common condition in the general population. However, the majority of HPV infections is subclinical and transitory and is resolved spontaneously. Intriguingly, viral oncogene expression, although necessary, is not per se sufficient to promote cervical cancer and other factors are involved in the progression of infected cells to the full neoplastic phenotype. In this perspective it has been suggested that the redox balance and the oxidative stress (OS) may represent interesting and under-explored candidates as promoting factors in HPV-initiated carcinogenesis.
  
  
  OBJECTIVE
  The current review discusses the possible interplay between the viral mechanisms modulating cell homeostasis and redox sensitive mechanisms. Experimental data and indirect evidences are presented on the activity of viral dependent functions on i) the regulation of enzymes and compounds involved in OS; ii) the protection from oxidation of detoxifying/antiapoptotic enzymes and redox-sensitive transcription factors; iii) the suppression of apoptosis; and iv) the modulation of host microRNAs regulating genes associated with antioxidant defense.
  
  
  CONCLUSIONS
  The resulting tangled scenario suggests that viral hosting cells adapt their metabolisms in order to support their growth and survival in the increasingly oxidant micro-environment associated with HPV tumor initiation and progression.
  
  
  CONCLUSIONS
  HPV can modulate the host cell redox homeostasis in order to favor infection and possibly tumor transformation. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.
authors.affiliation: Institute of Molecular Biology and Pathology, National Research Council, Rome, Italy.
authors.forename: Cesira
authors.initials: C
authors.lastname: Foppoli
authors.affiliation: Laboratory of Virology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: De Marco
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cini
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy. Electronic address: marzia.perluigi@uniroma1.it.
authors.forename: M
authors.initials: M
authors.lastname: Perluigi
mesh_terms: D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D008954:Models, Biological; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D010084:Oxidation-Reduction; D027383:Papillomaviridae / Q000378:metabolism* / Q000502:physiology; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D017382:Reactive Oxygen Species / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D009856:Oncogene Proteins, Viral; D017382:Reactive Oxygen Species
keywords: Antioxidant systems; Cervical cancer; Human papillomavirus; Oxidative stress; Transcription factors