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Intrinsic antiviral immunity of barrier cells revealed by an iPSC-derived blood-brain barrier cellular model.
Cheng, Yichen; Medina, Angelica; Yao, Zhenlan; Basu, Mausumi; Natekar, Janhavi P; Lang, Jianshe; Sanchez, Egan; Nkembo, Mezindia B; Xu, Chongchong; Qian, Xuyu; Nguyen, Phuong T T; Wen, Zhexing; Song, Hongjun; Ming, Guo-Li; Kumar, Mukesh; Brinton, Margo A; Li, Melody M H; Tang, Hengli.
Afiliação
  • Cheng Y; Department of Biological Science, Florida State University, Tallahassee, FL, USA.
  • Medina A; Department of Biological Science, Florida State University, Tallahassee, FL, USA.
  • Yao Z; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Basu M; Department of Biology, Georgia State University, Atlanta, GA, USA.
  • Natekar JP; Department of Biology, Georgia State University, Atlanta, GA, USA.
  • Lang J; Department of Biological Science, Florida State University, Tallahassee, FL, USA.
  • Sanchez E; Department of Biological Science, Florida State University, Tallahassee, FL, USA.
  • Nkembo MB; Department of Biological Science, Florida State University, Tallahassee, FL, USA.
  • Xu C; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
  • Qian X; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Nguyen PTT; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Wen Z; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
  • Song H; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Ming GL; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Kumar M; Department of Biology, Georgia State University, Atlanta, GA, USA.
  • Brinton MA; Department of Biology, Georgia State University, Atlanta, GA, USA.
  • Li MMH; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Tang H; Department of Biological Science, Florida State University, Tallahassee, FL, USA. Electronic address: tang@bio.fsu.edu.
Cell Rep ; 39(9): 110885, 2022 05 31.
Article em En | MEDLINE | ID: mdl-35649379
ABSTRACT
Physiological blood-tissue barriers play a critical role in separating the circulation from immune-privileged sites and denying access to blood-borne viruses. The mechanism of virus restriction by these barriers is poorly understood. We utilize induced pluripotent stem cell (iPSC)-derived human brain microvascular endothelial cells (iBMECs) to study virus-blood-brain barrier (BBB) interactions. These iPSC-derived cells faithfully recapitulate a striking difference in in vivo neuroinvasion by two alphavirus isolates and are selectively permissive to neurotropic flaviviruses. A model of cocultured iBMECs and astrocytes exhibits high transendothelial electrical resistance and blocks non-neurotropic flaviviruses from getting across the barrier. We find that iBMECs constitutively express an interferon-induced gene, IFITM1, which preferentially restricts the replication of non-neurotropic flaviviruses. Barrier cells from blood-testis and blood-retinal barriers also constitutively express IFITMs that contribute to the viral resistance. Our application of a renewable human iPSC-based model for studying virus-BBB interactions reveals that intrinsic immunity at the barriers contributes to virus exclusion.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Barreira Hematoencefálica / Células-Tronco Pluripotentes Induzidas Limite: Humans / Male Idioma: En Revista: Cell Rep Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Barreira Hematoencefálica / Células-Tronco Pluripotentes Induzidas Limite: Humans / Male Idioma: En Revista: Cell Rep Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos