ADAR1 function affects HPV replication and is associated to recurrent human papillomavirus-induced dysplasia in HIV coinfected individuals.
Por:
Pujantell M, Badia R, Galván-Femenía I, Garcia-Vidal E, de Cid R, Alcalde C, Tarrats A, Piñol M, Garcia F, Chamorro AM, Revollo B, Videla S, Parés D, Corral J, Tural C, Sirera G, Esté JA, Ballana E and Riveira-Muñoz E
Publicada:
27 dic 2019
Ahead of Print:
27 dic 2019
Categoría:
Multidisciplinary
Resumen:
Infection by human papillomavirus (HPV) alters the microenvironment of keratinocytes as a mechanism to evade the immune system. A-to-I editing by ADAR1 has been reported to regulate innate immunity in response to viral infections. Here, we evaluated the role of ADAR1 in HPV infection in vitro and in vivo. Innate immune activation was characterized in human keratinocyte cell lines constitutively infected or not with HPV. ADAR1 knockdown induced an innate immune response through enhanced expression of RIG-I-like receptors (RLR) signaling cascade, over-production of type-I IFNs and pro-inflammatory cytokines. ADAR1 knockdown enhanced expression of HPV proteins, a process dependent on innate immune function as no A-to-I editing could be identified in HPV transcripts. A genetic association study was performed in a cohort of HPV/HIV infected individuals followed for a median of 6 years (range 0.1-24). We identified the low frequency haplotype AACCAT significantly associated with recurrent HPV dysplasia, suggesting a role of ADAR1 in the outcome of HPV infection in HIV+ individuals. In summary, our results suggest that ADAR1-mediated innate immune activation may influence HPV disease outcome, therefore indicating that modification of innate immune effectors regulated by ADAR1 could be a therapeutic strategy against HPV infection.
Filiaciones:
:
AIDS Research Institute-IrsiCaixa, Badalona, Spain
Health Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain
:
AIDS Research Institute-IrsiCaixa, Badalona, Spain
Health Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain
:
Genomes for Life-GCAT Lab Group - Program of Predictive and Personalized Medicine of Cancer (PMPPC), Badalona, Spain
Health Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain
:
AIDS Research Institute-IrsiCaixa, Badalona, Spain
Health Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain
:
Genomes for Life-GCAT Lab Group - Program of Predictive and Personalized Medicine of Cancer (PMPPC), Badalona, Spain
Health Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain
Alcalde C:
Fundació Lluita contra la Sida, Hospital Germans Trias i Pujol, Badalona, Spain
:
Department of Gynecology, Hospital Germans Trias i Pujol, Badalona, Spain
:
Department of Surgery, Hospital Germans Trias i Pujol, Badalona, Spain
Garcia F:
Fundació Lluita contra la Sida, Hospital Germans Trias i Pujol, Badalona, Spain
Chamorro AM:
Fundació Lluita contra la Sida, Hospital Germans Trias i Pujol, Badalona, Spain
Revollo B:
Fundació Lluita contra la Sida, Hospital Germans Trias i Pujol, Badalona, Spain
Videla S:
Fundació Lluita contra la Sida, Hospital Germans Trias i Pujol, Badalona, Spain
:
Fundació Lluita contra la Sida, Hospital Germans Trias i Pujol, Badalona, Spain
Corral J:
Fundació Lluita contra la Sida, Hospital Germans Trias i Pujol, Badalona, Spain
:
Department of Internal Medicine, Hospital Germans Trias i Pujol, Badalona, Spain
:
Fundació Lluita contra la Sida, Hospital Germans Trias i Pujol, Badalona, Spain
Esté JA:
AIDS Research Institute-IrsiCaixa, Badalona, Spain.
Health Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain.
:
AIDS Research Institute-IrsiCaixa, Badalona, Spain
Health Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain
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