IFI16 DNA Sensor Is Required for Death of Lymphoid CD4 T-cells Abortively Infected with HIV

Details

• Alternative Title:
  Science
• Personal Author:
  Monroe, Kathryn M. ; Yang, Zhiyuan ; Johnson, Jeffrey R. ; Geng, Xin ; Doitsh, Gilad ; Krogan, Nevan J. ; Greene, Warner C.
• Description:
  The progressive depletion of quiescent "bystander" CD4 T cells, which are nonpermissive to HIV infection, is a principal driver of the acquired immunodeficiency syndrome (AIDS). These cells undergo abortive infection characterized by the cytosolic accumulation of incomplete HIV reverse transcripts. These viral DNAs are sensed by an unidentified host sensor that triggers an innate immune response, leading to caspase-1 activation and pyroptosis. Using unbiased proteomic and targeted biochemical approaches, as well as two independent methods of lentiviral short hairpin RNA-mediated gene knockdown in primary CD4 T cells, we identify interferon-γ-inducible protein 16 (IFI16) as a host DNA sensor required for CD4 T cell death due to abortive HIV infection. These findings provide insights into a key host pathway that plays a central role in CD4 T cell depletion during disease progression to AIDS.
• Subjects:
  Acquired Immunodeficiency Syndrome Apoptosis CD4-Positive T-Lymphocytes Cells, Cultured DNA, Viral DNA-Binding Proteins Gene Knockdown Techniques HEK293 Cells HIV-1 Humans Immunity, Innate Lymphocyte Depletion Nuclear Proteins Palatine Tonsil Phosphoproteins RNA, Small Interfering Spleen

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• Source:
  Science. 343(6169):428-432
• Pubmed ID:
  24356113
• Pubmed Central ID:
  PMC3976200
• Document Type:
  Journal Article
• Funding:
  1DP1036502/DP/NCCDPHP CDC HHSUnited States/ ; P50 GM081879/GM/NIGMS NIH HHSUnited States/ ; P50 GM082250/GM/NIGMS NIH HHSUnited States/ ; P30 AI027763/AI/NIAID NIH HHSUnited States/ ; R21 AI102782/AI/NIAID NIH HHSUnited States/ ; U19 AI096113/AI/NIAID NIH HHSUnited States/ ; DP1 DA036502/DA/NIDA NIH HHSUnited States/ ; P01 AI090935/AI/NIAID NIH HHSUnited States/
• Volume:
  343
• Issue:
  6169
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:78eb9cd49c67cbf6665837ebca7cdc8462c88dffb1de6d7a743d7a6345a74e35
• Download URL:
  https://stacks.cdc.gov/view/cdc/29908/cdc_29908_DS1.pdf
• File Type:
  [PDF - 595.81 KB ]