Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8(+) cells

doi:10.1038/s41586-020-1946-0

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-1946-0
	Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8(+) cells
	Diaz-Cuadros, Margarete 1,2; Wagner, Daniel E.3; Budjan, Christoph 1,2; Hubaud, Alexis 1,2; Tarazona, Oscar A.1,2; Donelly, Sophia 1,2; Michaut, Arthur 1,2; Al Tanoury, Ziad 1,2; Yoshioka-Kobayashi, Kumiko 4; Niino, Yusuke 5; Kageyama, Ryoichiro 4; Miyawaki, Atsushi 5; Touboul, Jonathan 6,7; Pourquie, Olivier 1,2,8
	2020-01-08
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	578 期号:7793 页码:154-+
文章类型	Article
语种	英语
国家	USA
英文关键词	Human immunodeficiency virus (HIV) persists indefinitely in individuals with HIV who receive antiretroviral therapy (ART) owing to a reservoir of latently infected cells that contain replication-competent virus(1-4). Here, to better understand the mechanisms responsible for latency persistence and reversal, we used the interleukin-15 superagonist N-803 in conjunction with the depletion of CD8(+) lymphocytes in ART-treated macaques infected with simian immunodeficiency virus (SIV). Although N-803 alone did not reactivate virus production, its administration after the depletion of CD8(+) lymphocytes in conjunction with ART treatment induced robust and persistent reactivation of the virus in vivo. We found viraemia of more than 60 copies per ml in all macaques (n = 14 100%) and in 41 out of a total of 56 samples (73.2%) that were collected each week after N-803 administration. Notably, concordant results were obtained in ART-treated HIV-infected humanized mice. In addition, we observed that co-culture with CD8(+) T cells blocked the in vitro latency-reversing effect of N-803 on primary human CD4(+) T cells that were latently infected with HIV. These results advance our understanding of the mechanisms responsible for latency reversal and lentivirus reactivation during ART-suppressed infection. The interleukin-15 superagonist N-803, combined with the depletion of CD8(+) lymphocytes, induced a robust and persistent reactivation of the virus in vivo in both antiretroviral-therapy-treated SIV-infected macaques and HIV-infected humanized mice.
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:000508801100008
WOS关键词	ANTIRETROVIRAL THERAPY ; LATENT RESERVOIR ; SUPPRESSION ; PLASMA ; BREAKTHROUGH ; REPLICATION ; DISULFIRAM ; EXPRESSION ; SIGNATURES ; INFECTION
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281491
专题	地球科学资源环境科学气候变化
作者单位	1.Harvard Med Sch, Dept Genet, Boston, MA 02115 USA; 2.Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA; 3.Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA; 4.Kyoto Univ, Inst Frontier Life & Med Sci, Kyoto, Japan; 5.RIKEN Ctr Brain Sci, Lab Cell Funct & Dynam, Saitama, Japan; 6.Brandeis Univ, Dept Math, Waltham, MA 02254 USA; 7.Brandeis Univ, Volen Natl Ctr Complex Syst, Waltham, MA USA; 8.Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA
推荐引用方式 GB/T 7714	Diaz-Cuadros, Margarete,Wagner, Daniel E.,Budjan, Christoph,et al. Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8(+) cells[J]. NATURE,2020,578(7793):154-+.
APA	Diaz-Cuadros, Margarete.,Wagner, Daniel E..,Budjan, Christoph.,Hubaud, Alexis.,Tarazona, Oscar A..,...&Pourquie, Olivier.(2020).Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8(+) cells.NATURE,578(7793),154-+.
MLA	Diaz-Cuadros, Margarete,et al."Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8(+) cells".NATURE 578.7793(2020):154-+.