RGD Reference Report - ADAR1 function affects HPV replication and is associated to recurrent human papillomavirus-induced dysplasia in HIV coinfected individuals. - Rat Genome Database

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ADAR1 function affects HPV replication and is associated to recurrent human papillomavirus-induced dysplasia in HIV coinfected individuals.

Authors: Pujantell, Maria  Badia, Roger  Galván-Femenía, Iván  Garcia-Vidal, Edurne  de Cid, Rafael  Alcalde, Carmen  Tarrats, Antonio  Piñol, Marta  Garcia, Francesc  Chamorro, Ana M  Revollo, Boris  Videla, Sebastian  Parés, David  Corral, Javier  Tural, Cristina  Sirera, Guillem  Esté, José A  Ballana, Ester  Riveira-Muñoz, Eva 
Citation: Pujantell M, etal., Sci Rep. 2019 Dec 27;9(1):19848. doi: 10.1038/s41598-019-56422-x.
RGD ID: 125097510
Pubmed: (View Article at PubMed) PMID:31882741
DOI: Full-text: DOI:10.1038/s41598-019-56422-x

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.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Adar  (adenosine deaminase, RNA-specific)

Genes (Mus musculus)
Adar  (adenosine deaminase, RNA-specific)

Genes (Homo sapiens)
ADAR  (adenosine deaminase RNA specific)


Additional Information