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Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice
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Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice
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Journal Article
Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice
2019
Overview
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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Anti-HIV Agents - pharmacology
/ Design
/ Funding
/ Genomes
/ HIV
/ HIV Infections - drug therapy
/ Human immunodeficiency virus
/ Humans
/ Luminescent Measurements - methods
/ Lymphoid Tissue - drug effects
/ Medicine
/ Medicine and Health Sciences
/ Mice
/ Proteins
/ Research and Analysis Methods
/ Software
/ Therapy
/ Tissues
/ Virus Replication - drug effects
/ Viruses
