IFI16 DNA Sensor Is Required for Death of Lymphoid CD4 T Cells Abortively Infected with HIV
Open accessAbstract
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.
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IFI16 binds and positively coactivates CASP1, which could trigger the inflammatory cascade to worsen Alzheimer's symptoms.
“Interestingly, IFI16, the product of the ADAOO accelerator gene IFI16 identified in our study, binds and positively coactivates CASP1, which could trigger the inflammatory cascade to worsen Alzheimer's symptoms.45”
From APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer’s disease (2016) · cites this paper as [45]
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- Authors
- Monroe, K. M., Yang, Z., Johnson, J. R., Geng, X., Doitsh, G., Krogan, N. J., & Greene, W. C.
- Affiliations
- Gladstone Institutes (US)
- QB3 (US)
- Corresponding author
- Monroe, Kathryn M.
- Yang, Zhiyuan
- Greene, Warner C.
- Venue
- Science
- Published
- 2014-01-24
- Volume
- 343
- Issue
- 6169
- Pages
- 428-432
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3976200
- OpenAlex
- W2079716935
- Cited by
- 511
- References
- 34
- Citations by year
- 2026: 16 · 2025: 21 · 2024: 35 · 2023: 28 · 2022: 34 · 2021: 40 · 2020: 34 · 2019: 30 · 2018: 48 · 2017: 38 · 2016: 53 · 2015: 67 · 2014: 65 · 2013: 2
- FWCI
- 28.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- A.P. Giannini Foundation
- Gladstone Institutes (P30AI027763)
- National Institutes of Health (AI 096113, AI027763, GM082250, GM081879)
- Center for AIDS Research, University of Washington (P30-AI027763)
- National Institute on Drug Abuse (DP1DA036502)
- National Institute of General Medical Sciences (P50GM082250, P50GM081879)
- National Institute of Allergy and Infectious Diseases (AI 090935, AI027763, P01AI090935, R21AI102782, AI-096113, U19AI096113, P30AI027763)
- National Center for Chronic Disease Prevention and Health Promotion (1DP1036502)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- IFI16, CD4+ T cell depletion, pyroptosis, caspase-1 activation, bystander T cells, innate immune response, AIDS, HIV disease progression
- MeSH terms
- Acquired Immunodeficiency Syndrome, Cells, Cultured, DNA-Binding Proteins, DNA, Viral, Humans, Immunity, Innate, Lymphocyte Depletion, Nuclear Proteins, Phosphoproteins, Spleen, Palatine Tonsil, CD4-Positive T-Lymphocytes, HIV-1, Apoptosis, RNA, Small Interfering, Gene Knockdown Techniques, HEK293 Cells
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