GSTDTAP  > 地球科学
DOI10.1038/s41586-020-1951-3
Systemic HIV and SIV latency reversal via non-canonical NF-kappa B signalling in vivo
Momcilovic, Milica; Jones, Anthony; Bailey, Sean T.; Waldmann, Christopher M.; Li, Rui; Lee, Jason T.1,2,3; Abdelhady, Gihad; Gomez, Adrian; Holloway, Travis; Schmid, Ernst; Stout, David; Fishbein, Michael C.; Stiles, Linsey; Dabir, Deepa V.; Dubinett, Steven M.; Christofk, Heather; Shirihai, Orian; Koehler, Carla M.; Sadeghi, Saman; Shackelford, David B.
2020-01-03
发表期刊NATURE
ISSN0028-0836
EISSN1476-4687
出版年2020
卷号578期号:7793页码:160-+
文章类型Article
语种英语
国家USA; Peoples R China; Canada
英文关键词

Activation of the non-canonical NF-kappa B signalling pathway by AZD5582 results in the induction of HIV and SIV RNA expression in the blood and tissues of antiretroviral-therapy-treated humanized mice and rhesus macaques.


Long-lasting, latently infected resting CD4(+) T cells are the greatest obstacle to obtaining a cure for HIV infection, as these cells can persist despite decades of treatment with antiretroviral therapy (ART). Estimates indicate that more than 70 years of continuous, fully suppressive ART are needed to eliminate the HIV reservoir(1). Alternatively, induction of HIV from its latent state could accelerate the decrease in the reservoir, thus reducing the time to eradication. Previous attempts to reactivate latent HIV in preclinical animal models and in clinical trials have measured HIV induction in the peripheral blood with minimal focus on tissue reservoirs and have had limited effect(2-9). Here we show that activation of the non-canonical NF-kappa B signalling pathway by AZD5582 results in the induction of HIV and SIV RNA expression in the blood and tissues of ART-suppressed bone-marrow-liver-thymus (BLT) humanized mice and rhesus macaques infected with HIV and SIV, respectively. Analysis of resting CD4(+) T cells from tissues after AZD5582 treatment revealed increased SIV RNA expression in the lymph nodes of macaques and robust induction of HIV in almost all tissues analysed in humanized mice, including the lymph nodes, thymus, bone marrow, liver and lung. This promising approach to latency reversal-in combination with appropriate tools for systemic clearance of persistent HIV infection-greatly increases opportunities for HIV eradication.


领域地球科学 ; 气候变化 ; 资源环境
收录类别SCI-E
WOS记录号WOS:000508801100012
WOS关键词CD4(+) T-CELLS ; VIRUS REACTIVATION ; INFECTED PATIENTS ; SMAC MIMETICS ; INHIBITOR ; SUPPRESSION ; PERSISTENCE ; EXPRESSION ; DISCOVERY ; PROVIDES
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
引用统计
被引频次:220[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/281450
专题地球科学
资源环境科学
气候变化
作者单位1.Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA;
2.Univ Calif Los Angeles, David Geffen Sch Med, Crump Inst Mol Imaging, Los Angeles, CA 90095 USA;
3.Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA
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GB/T 7714
Momcilovic, Milica,Jones, Anthony,Bailey, Sean T.,et al. Systemic HIV and SIV latency reversal via non-canonical NF-kappa B signalling in vivo[J]. NATURE,2020,578(7793):160-+.
APA Momcilovic, Milica.,Jones, Anthony.,Bailey, Sean T..,Waldmann, Christopher M..,Li, Rui.,...&Shackelford, David B..(2020).Systemic HIV and SIV latency reversal via non-canonical NF-kappa B signalling in vivo.NATURE,578(7793),160-+.
MLA Momcilovic, Milica,et al."Systemic HIV and SIV latency reversal via non-canonical NF-kappa B signalling in vivo".NATURE 578.7793(2020):160-+.
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