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

A critical barrier to the development of a human immunodeficiency virus (HIV) cure is the lack of an appropriate and scalable preclinical animal model that enables robust evaluation of candidate eradication approaches prior to testing in humans. Humanized mouse models typically involve engraftment of human fetal tissue and currently face ethical and political challenges. We established a fetal tissue-free humanized 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-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. J-Lat cells exhibited successful engraftment in several tissue sites, including spleen, bone barrow, peripheral blood, and lung, in line with the diverse tissue tropism of HIV in the human host. Administration of tumor necrosis factor (TNF)-α, an established HIV latency reversal agent, significantly induced GFP expression in engrafted cells across tissues (as measured by flow cytometry at necropsy), reflecting viral reactivation. These data suggest that the "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.