Publication Date:
2013-12-21
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-gamma-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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976200/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976200/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Monroe, Kathryn M -- Yang, Zhiyuan -- Johnson, Jeffrey R -- Geng, Xin -- Doitsh, Gilad -- Krogan, Nevan J -- Greene, Warner C -- 1DP1036502/DP/NCCDPHP CDC HHS/ -- DP1 DA036502/DA/NIDA NIH HHS/ -- P01 AI090935/AI/NIAID NIH HHS/ -- P30 AI027763/AI/NIAID NIH HHS/ -- P50 GM081879/GM/NIGMS NIH HHS/ -- P50 GM082250/GM/NIGMS NIH HHS/ -- R21 AI102782/AI/NIAID NIH HHS/ -- U19 AI096113/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Jan 24;343(6169):428-32. doi: 10.1126/science.1243640. Epub 2013 Dec 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24356113" target="_blank"〉PubMed〈/a〉
Keywords:
Acquired Immunodeficiency Syndrome/*immunology
;
Apoptosis/*immunology
;
CD4-Positive T-Lymphocytes/*immunology/*virology
;
Cells, Cultured
;
DNA, Viral/*immunology
;
DNA-Binding Proteins/genetics/immunology
;
Gene Knockdown Techniques
;
HEK293 Cells
;
HIV-1/*immunology
;
Humans
;
Immunity, Innate
;
Lymphocyte Depletion
;
Nuclear Proteins/genetics/*immunology
;
Palatine Tonsil/immunology
;
Phosphoproteins/genetics/*immunology
;
RNA, Small Interfering/genetics
;
Spleen/immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
