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PLoS Pathog. 2019 Dec 5;15(12):e1008161. doi: 10.1371/journal.ppat.1008161. eCollection 2019 Dec.

Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice.

Author information

1
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, United States of America.
2
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, United States of America.
3
Department of Cellular and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America.
4
School of Molecular and Cellular Biology, College of Liberal Arts and Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America.
5
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States of America.

Abstract

Non-invasive bioluminescent imaging (NIBLI) of HIV-1 infection dynamics allows for real-time monitoring of viral spread and the localization of infected cell populations in living animals. In this report, we describe full-length replication-competent GFP and Nanoluciferase (Nluc) expressing HIV-1 reporter viruses from two clinical transmitted / founder (T/F) strains: TRJO.c and Q23.BG505. By infecting humanized mice with these HIV-1 T/F reporter viruses, we were able to directly monitor longitudinal viral spread at whole-animal resolution via NIBLI at a sensitivity of as few as 30-50 infected cells. Bioluminescent signal strongly correlated with HIV-1 infection and responded proportionally to virus suppression in vivo in animals treated daily with a combination antiretroviral therapy (cART) regimen. Longitudinal NIBLI following cART withdrawal visualized tissue-sites that harbored virus during infection recrudescence. Notably, we observed rebounding infection in the same lymphoid tissues where infection was first observed prior to ART treatment. Our work demonstrates the utility of our system for studying in vivo viral infection dynamics and identifying infected tissue regions for subsequent analyses.

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