Abstract:
:Resting CD4+ T cells are highly resistant to the production of human immunodeficiency virus type 1 (HIV-1). However, the mechanism by which resting CD4+ T cells restrict such production in the late viral replication phase of infection has remained unclear. In this study, we found that the cell membrane metalloprotease TRAB domain-containing protein 2A (TRABD2A) inhibited this production in resting CD4+ T cells by degrading the virion structural precursor polyprotein Gag at the plasma membrane. Depletion or inhibition of metalloprotease activity by TRABD2A profoundly enhanced HIV-1 production in resting CD4+ T cells. TRABD2A expression was much higher in resting CD4+ T cells than in activated CD4+ T cells and was considerably reduced by T cell activation. Moreover, reexpressing TRABD2A reinforced the resistance of activated CD4+ T cells to the production of HIV-1 progeny. Collectively, these results elucidate the molecular mechanism employed by resting CD4+ T cells to potently restrict the assembly and production of HIV-1 progeny.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Liang G,Zhao L,Qiao Y,Geng W,Zhang X,Liu M,Dong J,Ding H,Sun H,Shang Hdoi
10.1038/s41590-019-0385-2subject
Has Abstractpub_date
2019-06-01 00:00:00pages
711-723issue
6eissn
1529-2908issn
1529-2916pii
10.1038/s41590-019-0385-2journal_volume
20pub_type
杂志文章abstract::The duration of T cell receptor (TCR) signaling is thought to be important for thymocyte differentiation into the CD4 or CD8 lineage. However, the in vivo relevance of this hypothesis is unclear. Here we divided T cell positive selection into genetically separable developmental steps by confining TCR signal transducti...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1040
更新日期:2004-03-01 00:00:00
abstract::In the version of this article initially published, the Supplementary Note was missing. The Supplementary Note has now been provided online and is cited in the Methods section of the article. The error has been corrected in the HTML and PDF version of the article. ...
journal_title:Nature immunology
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41590-018-0104-4
更新日期:2018-06-01 00:00:00
abstract::To investigate if the microRNA (miRNA) pathway is required for dendritic cell (DC) development, we assessed the effect of ablating Drosha and Dicer, the two enzymes central to miRNA biogenesis. We found that while Dicer deficiency had some effect, Drosha deficiency completely halted DC development and halted myelopoie...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3293
更新日期:2015-11-01 00:00:00
abstract::Oxidants such as H2O2 are connected to lymphocyte activation, but the molecular mechanisms behind this phenomenon are less clear. Here, I review data suggesting that by inhibiting protein tyrosine phosphatases, H2O2 plays an important role as a secondary messenger in the initiation and amplification of signaling at th...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1202-1129
更新日期:2002-12-01 00:00:00
abstract::The cellular dynamics of the egress of lymphocytes from lymph nodes are poorly defined. Here we visualized the branched organization of lymph node cortical sinuses and found that after entry, some T cells were retained, whereas others returned to the parenchyma. T cells deficient in sphingosine 1-phosphate receptor ty...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1682
更新日期:2009-01-01 00:00:00
abstract::In the version of this article initially published, the label (CASP4-C285A-HA) above the second and fifth lanes in the right blot in Fig. 1e is incorrect; the correct label is CASP4-C258A-HA. Also, the two labels at right above the plot in Fig. 6c were switched; the far right label should be 'Co-housed Serpinb1a-/-' (...
journal_title:Nature immunology
pub_type: 已发布勘误
doi:10.1038/s41590-019-0361-x
更新日期:2019-05-01 00:00:00
abstract::The metabolic challenges present in tumors attenuate the metabolic fitness and antitumor activity of tumor-infiltrating T lymphocytes (TILs). However, it remains unclear whether persistent metabolic insufficiency can imprint permanent T cell dysfunction. We found that TILs accumulated depolarized mitochondria as a res...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-0793-3
更新日期:2020-12-01 00:00:00
abstract::Ebola virus is a highly virulent pathogen capable of inducing a frequently lethal hemorrhagic fever syndrome. Accumulating evidence indicates that the virus actively subverts both innate and adaptive immune responses and triggers harmful inflammatory responses as it inflicts direct tissue damage. The host immune syste...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1519
更新日期:2007-11-01 00:00:00
abstract::The mechanisms that initiate T helper type 2 (T(H)2) responses are poorly understood. Here we demonstrate that cysteine protease-induced T(H)2 responses occur via 'cooperation' between migratory dermal dendritic cells (DCs) and basophils positive for interleukin 4 (IL-4). Subcutaneous immunization with papain plus ant...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1883
更新日期:2010-07-01 00:00:00
abstract::HPK1 is a Ste20-related serine-threonine kinase that inducibly associates with the adaptors SLP-76 and Gads after T cell receptor (TCR) signaling. Here, HPK1 deficiency resulted in enhanced TCR-induced phosphorylation of SLP-76, phospholipase C-gamma1 and the kinase Erk, more-persistent calcium flux, and increased pro...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1416
更新日期:2007-01-01 00:00:00
abstract::The molecular basis for the propensity of a small number of environmental proteins to provoke allergic responses is largely unknown. Herein, we report that mite group 13 allergens of the fatty acid-binding protein (FABP) family are sensed by an evolutionarily conserved acute-phase protein, serum amyloid A1 (SAA1), tha...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-0698-1
更新日期:2020-07-01 00:00:00
abstract::The detection of aberrant cells by natural killer (NK) cells is controlled by the integration of signals from activating and inhibitory ligands and from cytokines such as IL-15. We identified cytokine-inducible SH2-containing protein (CIS, encoded by Cish) as a critical negative regulator of IL-15 signaling in NK cell...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3470
更新日期:2016-07-01 00:00:00
abstract::The manner in which regulatory T cells (Treg cells) control lymphocyte homeostasis is not fully understood. We identified two Treg cell populations with differing degrees of self-reactivity and distinct regulatory functions. We found that GITR(hi)PD-1(hi)CD25(hi) (Triple(hi)) Treg cells were highly self-reactive and c...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3522
更新日期:2016-09-01 00:00:00
abstract::Infection of erythrocytes with Plasmodium species induces clinical malaria. Parasite-specific CD4(+) T cells correlate with lower parasite burdens and severity of human malaria and are needed to control blood-stage infection in mice. However, the characteristics of CD4(+) T cells that determine protection or parasite ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2180
更新日期:2011-12-11 00:00:00
abstract::According to current models of hematopoiesis, lymphoid-primed multi-potent progenitors (LMPPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)Flt3(hi)) and common myeloid progenitors (CMPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)CD41(hi)) establish an early branch point for separate lineage-commitment pathways from hematopoietic stem cells, wi...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3412
更新日期:2016-06-01 00:00:00
abstract::The extracellular protein Spätzle is required for activation of the Toll signaling pathway in the embryonic development and innate immune defense of Drosophila. Spätzle is synthesized as a pro-protein and is processed to a functional form by a serine protease. We show here that the mature form of Spätzle triggers a To...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni955
更新日期:2003-08-01 00:00:00
abstract::Toll-like receptor (TLR) signaling activates the inhibitor of transcription factor NF-κB (IκB) kinase (IKK) complex, which governs NF-κB-mediated transcription during inflammation. The RNase regnase-1 serves a critical role in preventing autoimmunity by controlling the stability of mRNAs that encode cytokines. Here we...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2137
更新日期:2011-10-30 00:00:00
abstract::The gammadelta T cells are prevalent in the mucosal epithelia and are postulated to act as 'sentries' for maintaining tissue integrity. What these gammadelta T cells recognize is poorly defined, but given the restricted T cell receptor (TCR) repertoire, the idea that they are selected by self antigens of low complexit...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1267
更新日期:2005-12-01 00:00:00
abstract::CD8(+) T cells eliminate intracellular infections through two contact-dependent effector functions: cytolysis and secretion of antiviral cytokines. Here we identify the following additional function for memory CD8(+) T cells that persist at front-line sites of microbial exposure: to serve as local sensors of previousl...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2568
更新日期:2013-05-01 00:00:00
abstract::Although approximately 200 viral microRNAs are known, only very few share similar targets with their host's microRNAs. A notable example of this is the stress-induced ligand MICB, which is targeted by several distinct viral and cellular microRNAs. Through the investigation of the microRNA-mediated immune-evasion strat...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1916
更新日期:2010-09-01 00:00:00
abstract::The Greek island of Crete became host to lively discussions on immunoregulation as experts from around the world gathered for the 7th Aegean Conference on Autoimmunity in September 2015. ...
journal_title:Nature immunology
pub_type:
doi:10.1038/ni.3367
更新日期:2016-03-01 00:00:00
abstract::The maintenance of immunological tolerance requires the deletion of self-reactive T cells in the thymus. The expression of genes encoding tissue-specific antigens (TSAs) by thymic epithelial cells is critical for this process and depends on activity of the transcriptional regulator Aire; however, the molecular mechani...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2820
更新日期:2014-03-01 00:00:00
abstract::The heterodimeric cytokine interleukin 27 (IL-27) signals through the IL-27Rα subunit of its receptor, combined with gp130, a common receptor chain used by several cytokines, including IL-6. Notably, the IL-27 subunits p28 (IL-27p28) and EBI3 are not always expressed together, which suggests that they may have unique ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1957
更新日期:2010-12-01 00:00:00
abstract::A20 is an anti-inflammatory protein that is strongly linked to human disease. Here, we find that mice expressing three distinct targeted mutations of A20's zinc finger 7 (ZF7) ubiquitin-binding motif uniformly developed digit arthritis with features common to psoriatic arthritis, while mice expressing point mutations ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-0634-4
更新日期:2020-04-01 00:00:00
abstract::Cytomegalovirus (CMV), measles and HIV are the main human pathogens known to induce immunosuppression. Unlike measles and HIV, and despite the availability of a well studied animal model, little is known about the mechanisms that control CMV-induced immunosuppression. We hypothesized that dendritic cells (DCs), which ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni724
更新日期:2001-11-01 00:00:00
abstract::Immune responses to microbial challenge in various tissues are not the same. Organ-specific immune responses are adapted to maintain organ physiology. ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni0107-3
更新日期:2007-01-01 00:00:00
abstract::The activation of an immune response requires recognition of microorganisms by host receptors. In drosophila, detection of Gram-positive bacteria is mediated by cooperation between the peptidoglycan-recognition protein-SA (PGRP-SA) and Gram-negative binding protein 1 (GNBP1) proteins. Here we show that some Gram-posit...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1123
更新日期:2004-11-01 00:00:00
abstract::Although the relationship between hematopoietic stem cells and progenitor populations has been investigated extensively under steady-state conditions, the dynamic response of the hematopoietic compartment during acute infection is largely unknown. Here we show that after infection of mice with Plasmodium chabaudi, a c...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1869
更新日期:2010-06-01 00:00:00
abstract::CD4+ T cell priming under T helper type I (T(H)1) or T(H)2 conditions gives rise to polarized cytokine gene expression. We found that in these conditions human naive T cells acquired stable histone hyperacetylation at either the Ifng or Il4 promoter. Effector memory T cells showed polarized cytokine gene acetylation p...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni872
更新日期:2003-01-01 00:00:00
abstract::Recent studies have highlighted the structural requirements for T cell costimulation and have revealed unusual modes of dimerization for the cytolytic T lymphocyte-associated antigen 4 (CTLA-4) costimulatory receptor and its B7 ligands. These distinctive quaternary structures potentially endow both receptor and ligand...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni0502-427
更新日期:2002-05-01 00:00:00