期刊
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
卷 16, 期 4, 页码 796-805出版社
SPRINGER
DOI: 10.1007/s11481-021-10011-w
关键词
Human immunodeficiency virus type one (HIV-1); Humanized mice; Adoptive transfer; Brain; Latent virus recovery; Mouse viral outgrowth assay
资金
- University of Nebraska Foundation
- National Institute of Health [R01MH115860, R01MH121402, R24OD018546]
The study demonstrates the persistence of HIV-1 infection in the brains of hu-HSC mice during long-term ART treatment using LA ART to suppress viral replication. The replicative HIV-1 reservoir established in the brains of hu-HSC mice was confirmed through cell transfer experiments, indicating the presence of a latent HIV-1 reservoir in the brain.
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.
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