μ-Lat: A mouse model to evaluate human immunodeficiency virus eradication strategies

被引：2

作者：

Sperber, Hannah S. ^{[1
,2
,3
]}

Togarrati, Padma Priya ^{[1
]}

Raymond, Kyle A. ^{[1
,3
]}

Bouzidi, Mohamed S. ^{[1
,3
]}

Gilfanova, Renata ^{[1
]}

Gutierrez, Alan G. ^{[1
]}

Muench, Marcus O. ^{[1
,3
]}

Pillai, Satish K. ^{[1
,3
]}

机构：

[1] Vitalant Res Inst, San Francisco, CA 94118 USA

[2] Free Univ Berlin, Inst Biochem, Berlin, Germany

[3] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA USA

来源：

FASEB JOURNAL | 2020年 / 34卷 / 11期

基金：

美国国家卫生研究院;

关键词：

antiviral gene therapy; humanized mouse; HIV; HIV latency; latency reversal; shock and kill; HUMAN IMMUNE-SYSTEM; IN-VIVO MODELS; SCID-HU MOUSE; MURINE MODEL; T-CELLS; CEREBROSPINAL-FLUID; HIV-1; INFECTION; TRANSGENIC MICE; MACROPHAGES; HEMATOPOIESIS;

D O I：

10.1096/fj.202001612RR

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A critical barrier to the development of a human immunodeficiency virus (HIV) cure is the lack of a scalable animal model that enables robust evaluation of eradication approaches prior to testing in humans. We established a humanized mouse model of latent HIV infection by transplanting "J-Lat" cells, Jurkat cells harboring a latent HIV provirus encoding an enhanced green fluorescent protein (GFP) reporter, into irradiated adult NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NSG) mice. J-Lat cells exhibited successful engraftment in several tissues including spleen, bone barrow, peripheral blood, and lung, in line with the diverse natural tissue tropism of HIV. Administration of tumor necrosis factor (TNF)-alpha, an established HIV latency reversal agent, significantly induced GFP expression in engrafted cells across tissues, reflecting viral reactivation. These data suggest that ourmurinelatency ("mu-Lat") model enables efficient determination of how effectively viral eradication agents, including latency reversal agents, penetrate, and function in diverse anatomical sites harboring HIV in vivo.

引用

页码：14615 / 14630

页数：16