High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Mediated Beta Interferon Expression

Persistent infection with some mucosal a-genus human papillomaviruses (HPVs; the most prevalent one being HPV16) can induce cervical carcinoma, anogenital cancers, and a subset of head and neck squamous cell carcinoma (HNSCC). Cutaneous β-genus HPVs (such as HPV5 and HPV8) associate with skin lesion...

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Detalles Bibliográficos
Autores: Poirson, Juline, Suarez, Irina Paula, Straub, Marie Laure, Cousido Siah, Alexandra, Peixoto, Paul, Hervouet, Eric, Foster, Anne, Mitschler, Andre, Mukobo, Noella, Chebaro, Yassmine, Garcin, Dominique, Recberlik, Sevda, Gaiddon, Christian, Altschuh, Daniele, Nomine, Yves, Podjarny, Alberto Daniel, Trave, Gilles, Masson, Murielle
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/214484
Acceso en línea:http://hdl.handle.net/11336/214484
Access Level:acceso abierto
Palabra clave:HPV
INTERACTOMIC
INTERFERONS
IRF3
THREE-DIMENSIONAL STRUCTURE
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descripción
Sumario:Persistent infection with some mucosal a-genus human papillomaviruses (HPVs; the most prevalent one being HPV16) can induce cervical carcinoma, anogenital cancers, and a subset of head and neck squamous cell carcinoma (HNSCC). Cutaneous β-genus HPVs (such as HPV5 and HPV8) associate with skin lesions that can progress into squamous cell carcinoma with sun exposure in Epidermodysplasia verruciformis patients and immunosuppressed patients. Here, we analyzed mechanisms used by E6 proteins from the a- and β-genus to inhibit the interferon-b (IFNB1) response. HPV16 E6 mediates this effect by a strong direct interaction with interferon regulatory factor 3 (IRF3). The binding site of E6 was localized within a flexible linker between the DNAbinding domain and the IRF-activation domain of IRF3 containing an LxxLL motif. The crystallographic structure of the complex between HPV16 E6 and the LxxLL motif of IRF3 was solved and compared with the structure of HPV16 E6 interacting with the LxxLL motif of the ubiquitin ligase E6AP. In contrast, cutaneous HPV5 and HPV8 E6 proteins bind to the IRF3-binding domain (IBiD) of the CREβ-binding protein (CBP), a key transcriptional coactivator in IRF3-mediated IFN-b expression.

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