μ-Lat: A Mouse Model to Evaluate Human Immunodeficiency Virus Eradication Strategies

Abstract

AbstractA 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-PrkdcscidIl2rgtm1Wjl/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.