Μ‐Lat: A mouse model to evaluate human immunodeficiency virus eradication strategies. Issue 11 (9th September 2020)

• Record Type: Journal Article
• Authors: Sperber, Hannah S.; Togarrati, Padma Priya; Raymond, Kyle A.; Bouzidi, Mohamed S.; Gilfanova, Renata; Gutierrez, Alan G.; Muench, Marcus O.; Pillai, Satish K.
• Is Part Of: FASEB journal. Volume 34:Issue 11(2020)
• Page Start: 14615
• Page End: 14630
• Publication Date: 2020-09-09
• Subjects: antiviral gene therapy -- humanized mouse -- HIV -- HIV latency -- latency reversal -- shock and kill; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202001612RR
• Languages: English
• ISSNs: 0892-6638

Abstract

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 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)‐α, an established HIV latency reversal agent, significantly induced GFP expression in engrafted cells across tissues, reflecting viral reactivation. These data suggest that our mu rine lat ency ("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.