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


Autoři: John D. Ventura aff001;  Jagadish Beloor aff002;  Edward Allen aff003;  Tongyu Zhang aff004;  Kelsey A. Haugh aff001;  Pradeep D. Uchil aff001;  Christina Ochsenbauer aff005;  Collin Kieffer aff004;  Priti Kumar aff002;  Thomas J. Hope aff003;  Walther Mothes aff001
Působiště autorů: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, United States of America aff001;  Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, United States of America aff002;  Department of Cellular and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America aff003;  School of Molecular and Cellular Biology, College of Liberal Arts and Sciences, University of Illinois at Urbana-Campaign, Urbana, IL, United States of America aff004;  Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States of America aff005
Vyšlo v časopise: Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008161
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008161

Souhrn

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) stains: 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.

Klíčová slova:

Blood plasma – Flow cytometry – HIV-1 – Infection imaging – Internal ribosome entry site – Reporter genes – Spleen – T cells


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Hygiena a epidemiologie Infekční lékařství Laboratoř

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