title: Interferon-induced gene expression in cervical mucosa during human papillomavirus infection.
abstract: The aim of this study is to monitor type I interferon (IFN) activation in the cervical mucosa of Human Papillomavirus (HPV)-infected and uninfected women attending a routine gynaecologic clinic. The expression of three IFN-induced genes (MxA coding for human Mixovirus resistance protein A, ISG15 Interferon Stimulated Gene coding for a 15 kDa ubiquitin-like protein and UBP43 coding for the ISG15 isopeptidase) was determined as the mRNA copy number in cervical cells, normalized to the mRNA ones of the beta-glucuronidase gene. Type-specific HPV-DNA load was concurrently determined in the HPV-positive samples. Out of 127 samples tested, 54 were sufficient for both DNA and RNA extraction. The type-specific HPV-DNA copy numbers in the 34 HPV-positive samples varied widely. No significant association was found between copy numbers of MxA, ISG15, UBP43 and HPV status or viral load. However, despite a marked inter-individual variability, ISG15 expression was significantly higher when low-risk HPV infections were compared with HPV-negative samples, while high-risk HPV infections had very low ISG15 levels. The lack of ISG15 activation in high-risk HPV-infected cervical cells could be due to the lack of p53-mediated induction or to HPV-directed specific inhibition of type I IFN pathways. This study approach might be of value in clarifying the role of type I IFN activation in determining the clearance or persistence of HPV infections.
authors.affiliation: Department of Molecular Medicine, Sapienza University, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pierangeli
authors.forename: A M
authors.initials: AM
authors.lastname: Degener
authors.forename: M L
authors.initials: ML
authors.lastname: Ferreri
authors.forename: E
authors.initials: E
authors.lastname: Riva
authors.forename: B
authors.initials: B
authors.lastname: Rizzo
authors.forename: O
authors.initials: O
authors.lastname: Turriziani
authors.forename: S
authors.initials: S
authors.lastname: Luciani
authors.forename: C
authors.initials: C
authors.lastname: Scagnolari
authors.forename: G
authors.initials: G
authors.lastname: Antonelli
mesh_terms: D000293:Adolescent; D000328:Adult; D002584:Cervix Uteri / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis; D010450:Endopeptidases / Q000235:genetics; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007370:Interferon Type I / Q000502:physiology*; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology* / Q000821:virology; D064547:Myxovirus Resistance Proteins; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis; D043222:Ubiquitin Thiolesterase; D014452:Ubiquitins / Q000235:genetics; D019562:Viral Load
chemical_list: D016207:Cytokines; D004279:DNA, Viral; D007370:Interferon Type I; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D014452:Ubiquitins; C074034:ISG15 protein, human; D010450:Endopeptidases; C485560:USP18 protein, human; D043222:Ubiquitin Thiolesterase; D019204:GTP-Binding Proteins