Your browser doesn't support javascript.
loading
Restriction factor compendium for influenza A virus reveals a mechanism for evasion of autophagy.
Martin-Sancho, Laura; Tripathi, Shashank; Rodriguez-Frandsen, Ariel; Pache, Lars; Sanchez-Aparicio, Maite; McGregor, Michael J; Haas, Kelsey M; Swaney, Danielle L; Nguyen, Thong T; Mamede, João I; Churas, Christopher; Pratt, Dexter; Rosenthal, Sara B; Riva, Laura; Nguyen, Courtney; Beltran-Raygoza, Nish; Soonthornvacharin, Stephen; Wang, Guojun; Jimenez-Morales, David; De Jesus, Paul D; Moulton, Hong M; Stein, David A; Chang, Max W; Benner, Chris; Ideker, Trey; Albrecht, Randy A; Hultquist, Judd F; Krogan, Nevan J; García-Sastre, Adolfo; Chanda, Sumit K.
Afiliação
  • Martin-Sancho L; Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
  • Tripathi S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Rodriguez-Frandsen A; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Pache L; Center for Infectious Disease Research, Microbiology & Cell Biology Department, Indian Institute of Science, Bangalore, India.
  • Sanchez-Aparicio M; Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
  • McGregor MJ; Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
  • Haas KM; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Swaney DL; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Nguyen TT; Quantitative Biosciences Institute (QBI), University of California, San Francisco, CA, USA.
  • Mamede JI; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • Churas C; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA.
  • Pratt D; Quantitative Biosciences Institute (QBI), University of California, San Francisco, CA, USA.
  • Rosenthal SB; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • Riva L; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA.
  • Nguyen C; Quantitative Biosciences Institute (QBI), University of California, San Francisco, CA, USA.
  • Beltran-Raygoza N; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • Soonthornvacharin S; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA.
  • Wang G; Quantitative Biosciences Institute (QBI), University of California, San Francisco, CA, USA.
  • Jimenez-Morales D; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
  • De Jesus PD; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA.
  • Moulton HM; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL, USA.
  • Stein DA; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Chang MW; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Benner C; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Ideker T; Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
  • Albrecht RA; Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
  • Hultquist JF; Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
  • Krogan NJ; Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
  • García-Sastre A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Chanda SK; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nat Microbiol ; 6(10): 1319-1333, 2021 10.
Article em En | MEDLINE | ID: mdl-34556855
ABSTRACT
The fate of influenza A virus (IAV) infection in the host cell depends on the balance between cellular defence mechanisms and viral evasion strategies. To illuminate the landscape of IAV cellular restriction, we generated and integrated global genetic loss-of-function screens with transcriptomics and proteomics data. Our multi-omics analysis revealed a subset of both IFN-dependent and independent cellular defence mechanisms that inhibit IAV replication. Amongst these, the autophagy regulator TBC1 domain family member 5 (TBC1D5), which binds Rab7 to enable fusion of autophagosomes and lysosomes, was found to control IAV replication in vitro and in vivo and to promote lysosomal targeting of IAV M2 protein. Notably, IAV M2 was observed to abrogate TBC1D5-Rab7 binding through a physical interaction with TBC1D5 via its cytoplasmic tail. Our results provide evidence for the molecular mechanism utilised by IAV M2 protein to escape lysosomal degradation and traffic to the cell membrane, where it supports IAV budding and growth.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vírus da Influenza A / Autofagia / Evasão da Resposta Imune Limite: Humans Idioma: En Revista: Nat Microbiol Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vírus da Influenza A / Autofagia / Evasão da Resposta Imune Limite: Humans Idioma: En Revista: Nat Microbiol Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos