Transcriptional Mapping of Neuro-Immune Interactions during Homeostasis and HIV infection using Microglia-containing Human Cerebral Assembloids

A Human iPSC-Derived Tri-Culture Model of NeuroHIV: HIV Infection, Antiretroviral Drug Effects, Microglial Morphology, and Neuronal Calcium Dynamics

HIV-associated neurocognitive disorders (HAND) can persist despite effective ART and are associated with persistent central nervous system (CNS) viral reservoirs in microglia, chronic neuroinflammation, synaptic dysfunction, and neuronal injury. Thus, human-relevant multicellular CNS models are needed to elucidate neur...

SPP1+ Microglia Are Associated with Neuroimmune Rewiring and Glutamatergic Neuronal Injury in ART-Suppressed People Living with HIV

Antiretroviral therapy (ART) effectively suppresses systemic HIV replication but does not eradicate viral reservoirs in the brain, where their identity and contribution to neurological injury remain poorly defined. Using bulk, single-cell, and single-nucleus transcriptomics of postmortem human brain tissue, we identify...

HIV-1 Tat and gp120 as key drivers of neurodegeneration in the central nervous system

Converging data achieved from in vitro models, Tat and gp120-transgenic mice, post-mortem tissue, and cerebrospinal fluid biomarkers indicate that these viral proteins contribute to frontostriatal atrophy and hybrid HAND-AD phenotypes increasingly observed in aging HIV patients.

A critical in vivo role for microglial p38α MAPK in HIV-1 associated inflammatory brain injury.

People with HIV (PWH) develop neurocognitive impairment despite control of viral infection. Key pathological features of NeuroHIV patients, including activated microglia, neuronal damage and behavioral impairment, are present in transgenic mice expressing HIV-1 envelope glycoprotein gp120 in their brain (HIVgp120tg). H...

Comparative Investigation of Immunopathogenesis in HIV-and Mycobacterium Tuberculosis Single Infection Versus Co-Infection Using Humanized Mice

NF-κB-dependent and independent inflammatory responses during acute HIV-1 infection in a model of human microglia

Introduction Microglia are the main targets of HIV-1 infection in the central nervous system (CNS) and are considered important contributors to chronic neuroinflammation in people living with HIV (PLWH). In this study, we investigated the mechanisms leading to inflammatory responses during acute HIV-1 infection in an a...