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Front. Immunol. | doi: 10.3389/fimmu.2018.00344

Ultra-sensitive HIV-1 latency viral outgrowth assays using humanized mice

  • 1Colorado State University, United States

In the current quest for a complete cure for HIV/AIDS, highly sensitive HIV latency detection methods are critical to verify full viral eradication. Until now, the in vitro quantitative viral out growth assays (qVOA) have been the gold standard for assessing latent HIV-1 viral burden. However, these assays have been inadequate in detecting the presence of ultra-low levels of latent virus in a number of patients who were initially thought to have been cured but eventually showed viral rebound. In this context, new approaches utilizing in vivo mouse-based VOAs are promising. In the murine VOA (mVOA), large numbers of CD4+ T cells or PBMC from aviremic subjects are xenografted into immunodeficient NSG mice whereas in the humanized mouse VOA (hmVOA) assay, patient CD4+ T cell samples are injected into BLT or hu-HSC humanized mice. While latent virus could be recovered in both of these systems, the hmVOA provides higher sensitivity than the mVOA using fewer number of input cells. In contrast to the mVOA, the hmVOA provides a broader spectrum of highly susceptible HIV-1 target cells and enables newly engrafted cells to home into preformed human lymphoid organs where they can infect cells in situ after viral activation. Hu-mice also allow for both xenograft and allograft driven cell expansion with less severe GvH providing a longer time frame for potential viral outgrowth from cells with a delayed latent viral activation. Based on these advantages, the hmVOA has great potential in playing an important role in HIV latency and cure research.

Keywords: HIV-1 latent viral outgrowth assay using humanized mice, Humanized mouse-based HIV-1 latency outgrowth assay, Comparison of qVOA with humanized mouse-based viral outgrowth assay, Comparison of mVOA with hmVOA, NHP-based latent SIV viral outgrowth assay, Sensitivity of hmVOA over mVOA, Ultrasensitive HIV-1 latent VOA in hu-mice, Mouse-based HIV-1 VOA

Received: 14 Dec 2017; Accepted: 07 Feb 2018.

Edited by:

Jeffrey K. Actor, University of Texas Health Science Center at Houston, United States

Reviewed by:

James Di Santo, Institut Pasteur, France
Mangala Rao, United States Military HIV Research Program, United States  

Copyright: © 2018 Schmitt and Akkina. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Ramesh Akkina, Colorado State University, Fort Collins, United States, akkina@colostate.edu