Adult human brain tissue cultures to study neuroHIV DOI Open Access
Rachel Van Duyne,

Elena Irollo,

Angel Lin

et al.

Published: April 19, 2024

HIV-associated neurocognitive disorders (HAND) persist under antiretroviral therapy as a complex pathology that has been difficult to study in cellular and animal models. Therefore, we generated an ex vivo human brain slice model of HIV-1 infection from surgically resected adult tissue. Brain cultures processed for flow cytometry showed >90% viability dissoci-ated cells within the first three weeks vitro, with parallel detection astrocyte, myeloid, neuronal populations. Neurons slices stable dendritic spine density mature morphologies culture, they detectable activity multi-electrode arrays. We infected cultured using patient-matched CD4+ T-cells or monocyte-derived macrophages (MDMs) were exposed GFP-expressing R5-tropic vitro. Infected expressed viral RNA developed spreading up 9-days post-infection, which significantly decreased by antiretrovirals. also detected myeloid astrocytes observed minimal effect on via-bility over time. Overall, this human-centered offers promising resource cel-lular mechanisms contributing HAND (including toxicity, substance use, aging), resident cells, new neuroprotective therapeutics.

Language: Английский

Adult human brain tissue cultures to study neuroHIV DOI Open Access
Rachel Van Duyne,

Elena Irollo,

Angel Lin

et al.

Published: April 19, 2024

HIV-associated neurocognitive disorders (HAND) persist under antiretroviral therapy as a complex pathology that has been difficult to study in cellular and animal models. Therefore, we generated an ex vivo human brain slice model of HIV-1 infection from surgically resected adult tissue. Brain cultures processed for flow cytometry showed >90% viability dissoci-ated cells within the first three weeks vitro, with parallel detection astrocyte, myeloid, neuronal populations. Neurons slices stable dendritic spine density mature morphologies culture, they detectable activity multi-electrode arrays. We infected cultured using patient-matched CD4+ T-cells or monocyte-derived macrophages (MDMs) were exposed GFP-expressing R5-tropic vitro. Infected expressed viral RNA developed spreading up 9-days post-infection, which significantly decreased by antiretrovirals. also detected myeloid astrocytes observed minimal effect on via-bility over time. Overall, this human-centered offers promising resource cel-lular mechanisms contributing HAND (including toxicity, substance use, aging), resident cells, new neuroprotective therapeutics.

Language: Английский

Citations

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