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

• DOI: 10.1007/s11481-021-10011-w
• Publication Date: 2021-09-15T16:03:13Z
• Authors: Hang Su; Sruthi Sravanam; Brady Sillman; Emiko Waight; Edward Makarov; Saumi Mathews; Larisa Y. Poluektova; Santhi Gorantla; Howard E. Gendelman; Prasanta K. Dash
• Keywords: CD4-Positive T-Lymphocytes; 0303 health sciences; Brain; HIV Infections; Viral Load; Virus Replication; Adoptive Transfer; Article; Virus Latency; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; HIV-1; Animals

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.