Recovery of Latent HIV-1 from Brain Tissue by Adoptive Cell Transfer in Virally Suppressed Humanized Mice

Hang Su, Sruthi Sravanam, Brady Sillman, Emiko Waight, Edward Makarov, Saumi Mathews, Larisa Y. Poluektova, Santhi Gorantla, Howard E. Gendelman, Prasanta K. Dash

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Defining the latent human immunodeficiency virus type 1 (HIV-1) burden in the human brain during progressive infection is limited by sample access. Human hematopoietic stem cells (hu-HSCs)-reconstituted humanized mice provide an opportunity for this study. The model mimics, in measure, HIV-1 pathophysiology, transmission, treatment, and elimination in an infected human host. However, to date, brain HIV-1 latency in hu-HSC mice during suppressive antiretroviral therapy (ART) was not studied. To address this need, hu-HSC mice were administered long acting (LA) ART 14 days after HIV-1 infection was established. Animals were maintained under suppressive ART for 3 months, at which time HIV-1 infection was detected at low levels in brain tissue by droplet digital polymerase chain reaction (ddPCR) test on DNA. Notably, adoptive transfer of cells acquired from the hu-HSC mouse brains and placed into naive hu-HSC mice demonstrated viral recovery. These proof-of-concept results demonstrate replication-competent HIV-1 reservoir can be established in hu-HSC mouse brains that persists during long-term ART treatment. Hu-HSC mice-based mouse viral outgrowth assay (hu-MVOA) serves as a sensitive tool to interrogate latent HIV-1 brain reservoirs. Graphic Abstract: [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)796-805
Number of pages10
JournalJournal of Neuroimmune Pharmacology
Volume16
Issue number4
DOIs
StatePublished - Dec 2021

Keywords

  • Adoptive transfer
  • Brain
  • Human immunodeficiency virus type one (HIV-1)
  • Humanized mice
  • Latent virus recovery
  • Mouse viral outgrowth assay

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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