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Induction of necroptotic cell death by viral activation of the RIG-I or STING pathway.
Schock, Suruchi N; Chandra, Neha V; Sun, Yuefang; Irie, Takashi; Kitagawa, Yoshinori; Gotoh, Bin; Coscoy, Laurent; Winoto, Astar.
Afiliação
  • Schock SN; Department of Molecular and Cell Biology and Cancer Research Laboratory, 469 LSA, University of California, Berkeley, CA 94720-3200, USA.
  • Chandra NV; Department of Molecular and Cell Biology and Cancer Research Laboratory, 469 LSA, University of California, Berkeley, CA 94720-3200, USA.
  • Sun Y; Department of Molecular and Cell Biology and Cancer Research Laboratory, 469 LSA, University of California, Berkeley, CA 94720-3200, USA.
  • Irie T; Department of Virology, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
  • Kitagawa Y; Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan.
  • Gotoh B; Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan.
  • Coscoy L; Department of Molecular and Cell Biology and Cancer Research Laboratory, 469 LSA, University of California, Berkeley, CA 94720-3200, USA.
  • Winoto A; Department of Molecular and Cell Biology and Cancer Research Laboratory, 469 LSA, University of California, Berkeley, CA 94720-3200, USA.
Cell Death Differ ; 24(4): 615-625, 2017 04.
Article em En | MEDLINE | ID: mdl-28060376
ABSTRACT
Necroptosis is a form of necrotic cell death that requires the activity of the death domain-containing kinase RIP1 and its family member RIP3. Necroptosis occurs when RIP1 is deubiquitinated to form a complex with RIP3 in cells deficient in the death receptor adapter molecule FADD or caspase-8. Necroptosis may play a role in host defense during viral infection as viruses like vaccinia can induce necroptosis while murine cytomegalovirus encodes a viral inhibitor of necroptosis. To see how general the interplay between viruses and necroptosis is, we surveyed seven different viruses. We found that two of the viruses tested, Sendai virus (SeV) and murine gammaherpesvirus-68 (MHV68), are capable of inducing dramatic necroptosis in the fibrosarcoma L929 cell line. We show that MHV68-induced cell death occurs through the cytosolic STING sensor pathway in a TNF-dependent manner. In contrast, SeV-induced death is mostly independent of TNF. Knockdown of the RNA sensing molecule RIG-I or the RIP1 deubiquitin protein, CYLD, but not STING, rescued cells from SeV-induced necroptosis. Accompanying necroptosis, we also find that wild type but not mutant SeV lacking the viral proteins Y1 and Y2 result in the non-ubiquitinated form of RIP1. Expression of Y1 or Y2 alone can suppress RIP1 ubiquitination but CYLD is dispensable for this process. Instead, we found that Y1 and Y2 can inhibit cIAP1-mediated RIP1 ubiquitination. Interestingly, we also found that SeV infection of B6 RIP3-/- mice results in increased inflammation in the lung and elevated SeV-specific T cells. Collectively, these data identify viruses and pathways that can trigger necroptosis and highlight the dynamic interplay between pathogen-recognition receptors and cell death induction.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Gammaherpesvirinae / Vírus Sendai / Proteína DEAD-box 58 / Proteínas de Membrana Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Death Differ Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Gammaherpesvirinae / Vírus Sendai / Proteína DEAD-box 58 / Proteínas de Membrana Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Death Differ Ano de publicação: 2017 Tipo de documento: Article