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

John D. Ventura, Jagadish Beloor, Edward Allen, Tongyu Zhang, Kelsey A. Haugh, Pradeep D. Uchil, Christina Ochsenbauer, Collin Kieffer, Priti Kumar, Thomas J. Hope, Walther Mothes

Research output: Contribution to journalArticle

Abstract

Non-invasive bioluminescent imaging (NIBLI) of HIV-1 infection dynamics allows for realtime 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.

Original languageEnglish (US)
Article numbere1008161
JournalPLoS pathogens
Volume15
Issue number12
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Fingerprint Dive into the research topics of 'Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice'. Together they form a unique fingerprint.

  • Cite this

    Ventura, J. D., Beloor, J., Allen, E., Zhang, T., Haugh, K. A., Uchil, P. D., Ochsenbauer, C., Kieffer, C., Kumar, P., Hope, T. J., & Mothes, W. (2019). Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice. PLoS pathogens, 15(12), [e1008161]. https://doi.org/10.1371/journal.ppat.1008161