A humanized mouse-based HIV-1 viral outgrowth assay with higher sensitivity than in vitro qVOA in detecting latently infected cells from individuals on ART with undetectable viral loads

作者：Charlins Paige; Schmitt Kimberly; Remling Mulder Leila; Hogan Louise E; Hanhauser Emily; Hobbs Kristen S; Hecht Frederick; Deeks Steven G; Henrich Timothy J; Akkina Ramesh^*

来源：Virology, 2017, 507: 135-139.

DOI：10.1016/j.viro1.2017.04.011

• Humanized mouse-based latent HIV-1 viral outgrowth assay
• In vivo latent HIV-1 viral outgrowth assay
• Comparison of HIV qVOA and in vivo humouse VOA
• Ultra-Sensitive latent HIV-1 detection in patient cells
• Latent HIV-1 detection by hu-mouse-based VOA

Assays that can verify full viral eradication are essential in the context of achieving a cure for HIV/AIDS. In vitro quantitative viral out growth assays (qVOA) are currently the gold standard for measuring latent HIV-1 but these assays often fail to detect very low levels of replication-competent virus. Here we investigated an alternative in vivo approach for sensitive viral detection using humanized mice (hmVOA). Peripheral blood CD4+ T cell samples from HIV subjects on stable ART with undetectable viral loads by RT-PCR were first assayed by in vitro qVOA. Corresponding patient samples in which no virus was detected by qVOA were injected into humanized mice to allow viral outgrowth. Of the five qVOA virus negative samples, four gave positive viral outgrowth in the hmVOA assay suggesting that it is more sensitive in detecting latent HIV-1.

• 出版日期2017-7