Next-Generation Human Cerebral Organoids as Powerful Tools To Advance NeuroHIV Research

mBio

卷:12

Susana T. Valente¹  Ana Leda¹  Sonia Mediouni¹  Robert L. Furler²  Douglas F. Nixon²  Lishomwa C. Ndhlovu²  Thomas A. Premeaux²  Howard A. Fine³ 

[1] Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA;

[2] Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA;

[3] Meyer Cancer Center, Division of Neuro-Oncology, Department of Neurology, New York-Presbyterian Hospital/Weill Cornell Medicine, New York, New York, USA;

关键词: cerebral organoids;    HIV reservoirs;    HIV cure;    neuropathology;    cure;    HIV;   

DOI  :  10.1128/mBio.00680-21

来源: DOAJ

【 摘 要 】

ABSTRACT Long-term effective use of antiretroviral therapy (ART) among people with HIV (PWH) has significantly reduced the burden of disease, yet a cure for HIV has not been universally achieved, likely due to the persistence of an HIV reservoir. The central nervous system (CNS) is an understudied HIV sanctuary. Importantly, due to viral persistence in the brain, cognitive disturbances persist to various degrees at high rates in PWH despite suppressive ART. Given the complexity and accessibility of the CNS compartment and that it is a physiologically and anatomically unique immune site, human studies to reveal molecular mechanisms of viral entry, reservoir establishment, and the cellular and structural interactions leading to viral persistence and brain injury to advance a cure and either prevent or limit cognitive impairments in PWH remain challenging. Recent advances in human brain organoids show that they can mimic the intercellular dynamics of the human brain and may recapitulate many of the events involved in HIV infection of the brain (neuroHIV). Human brain organoids can be produced, spontaneously or with addition of growth factors and at immature or mature states, and have become stronger models to study neurovirulent viral infections of the CNS. While organoids provide opportunities to study neuroHIV, obstacles such as the need to incorporate microglia need to be overcome to fully utilize this model. Here, we review the current achievements in brain organoid biology and their relevance to neuroHIV research efforts.

【 授权许可】

Unknown