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μ-Lat: A mouse model to evaluate human immunodeficiency virus eradication strategies.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2020 Nov; Vol. 34 (11), pp. 14615-14630. Date of Electronic Publication: 2020 Sep 09. - Publication Year :
- 2020
-
Abstract
- 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 <superscript>scid</superscript> Il2rg <superscript>tm1Wjl</superscript> /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)-α, an established HIV latency reversal agent, significantly induced GFP expression in engrafted cells across tissues, reflecting viral reactivation. These data suggest that our murine latency ("μ-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.<br /> (© 2020 Federation of American Societies for Experimental Biology.)
- Subjects :
- Animals
Bone Marrow virology
Female
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
HIV genetics
HIV pathogenicity
HIV Infections pathology
HIV Infections therapy
Humans
Jurkat Cells
Lung virology
Male
Mice
Mice, Inbred NOD
Proviruses genetics
Spleen virology
Transfection methods
Cell Transplantation methods
Disease Models, Animal
HIV physiology
HIV Infections virology
Virus Latency
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 34
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 32901981
- Full Text :
- https://doi.org/10.1096/fj.202001612RR