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Ubiquitin-Conjugating Enzyme E2 L3 is Downregulated by the Chikungunya Virus nsP2 Protease.
Ramphan, Suwipa; Khongwichit, Sarawut; Saisawang, Chonticha; Kovanich, Duangnapa; Ketterman, Albert J; Ubol, Sukathida; Auewarakul, Prasert; Roytrakul, Sittiruk; Smith, Duncan R; Kuadkitkan, Atichat.
Afiliación
  • Ramphan S; Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.
  • Khongwichit S; Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.
  • Saisawang C; Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.
  • Kovanich D; Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.
  • Ketterman AJ; Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.
  • Ubol S; Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
  • Auewarakul P; Center for Emerging and Neglected Infectious Diseases, Mahidol University, Nakhon Pathom, Thailand.
  • Roytrakul S; Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  • Smith DR; National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand.
  • Kuadkitkan A; Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.
Proteomics Clin Appl ; 12(4): e1700020, 2018 07.
Article en En | MEDLINE | ID: mdl-28975709
PURPOSE: Chikungunya virus (CHIKV) is a mosquito transmitted alphavirus that causes chikungunya fever in humans. The CHIKV non-structural protein 2 (nsP2) is a multifunctional protein that additionally modulates the host cell to dampen the innate immune response and inhibit other cellular processes. EXPERIMENTAL DESIGN: To further investigate the interactions of nsP2 with host cells, the protease domain of CHIKV nsP2 (nsP2-pro) is transfected into Hela cells, and differential protein expression is detected by 2D polyacrylamide gel electrophoresis. RESULTS: A total of 21 differentially regulated (six upregulated, 15 downregulated) spots are observed, of which five are identified by mass spectrometry. The downregulation of one of the identified proteins, ubiquitin-conjugating enzyme E2 L3 (UBE2L3) is confirmed by western blotting of both nsP2-pro transfection and CHIKV natural infection, and the downregulation of UBE2L3 is additionally shown to require an enzymatically active nsP2 protease domain. Transfection of full length UBE2L3 into HEK293T/17 cells prior to CHIKV infection reduce levels of infection and E protein expression but do not alter RNA genome levels. CONCLUSION: These results suggest that UBE2L3 is a cellular target of the CHIKV nsP2 protease, and this possibly mediates the pathogenesis of chikungunya fever.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Replicación Viral / Cisteína Endopeptidasas / Virus Chikungunya / Enzimas Ubiquitina-Conjugadoras / Fiebre Chikungunya Límite: Humans Idioma: En Revista: Proteomics Clin Appl Asunto de la revista: BIOQUIMICA Año: 2018 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Replicación Viral / Cisteína Endopeptidasas / Virus Chikungunya / Enzimas Ubiquitina-Conjugadoras / Fiebre Chikungunya Límite: Humans Idioma: En Revista: Proteomics Clin Appl Asunto de la revista: BIOQUIMICA Año: 2018 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Alemania