Ultra-Sensitive HIV-1 Latency Viral Outgrowth Assays Using Humanized Mice

• Published in: Frontiers in immunology Vol. 9; p. 344
• Main Authors: Schmitt, Kimberly, Akkina, Ramesh
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 05.03.2018
• Subjects: Acquired Immunodeficiency Syndrome - immunology; Animals; Biological Assay - methods; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - transplantation; CD4-Positive T-Lymphocytes - virology; comparison of mVOA with humanized mouse-based viral outgrowth assay; comparison of quantitative viral outgrowth assays with humanized mouse-based viral outgrowth assay; Heterografts; HIV-1 - physiology; HIV-1 latent viral outgrowth assay using humanized mice; humanized mouse-based HIV-1 latency outgrowth assay; Humans; Immunology; Mice; non-human primate-based latent simian immunodeficiency viral outgrowth assay; sensitivity of humanized mouse-based viral outgrowth assay over mVOA; Virus Activation - immunology; Virus Latency - immunology; comparison of quantitative viral outgrowth assays with humanized mouse-based viral outgrowth assay; ultra-sensitive HIV-1 latent viral outgrowth assay in hu-mice; sensitivity of humanized mouse-based viral outgrowth assay over mVOA; humanized mouse-based HIV-1 latency outgrowth assay; non-human primate-based latent simian immunodeficiency viral outgrowth assay; mouse-based HIV-1 viral outgrowth assays; comparison of mVOA with humanized mouse-based viral outgrowth assay; HIV-1 latent viral outgrowth assay using humanized mice
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.00344

In the current quest for a complete cure for HIV/AIDS, highly sensitive HIV-1 latency detection methods are critical to verify full viral eradication. Until now, the quantitative viral outgrowth 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 ultralow 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 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-based VOA (hmVOA) patient CD4 T cell samples are injected into BLT or hu-hematopoetic stem cells (hu-HSC) humanized mice. While latent virus could be recovered in both of these systems, the hmVOA provides higher sensitivity than the mVOA using a 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 after viral activation. Hu-mice also allow for both xenograft- and allograft-driven cell expansions 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-1 latency and cure research.