Abstract
Brain organoids, or brainoids, have shown great promise in the study of central nervous system (CNS) infection. Modeling Zika virus (ZIKV) infection in brain organoids may help elucidate the relationship between ZIKV infection and microcephaly. Brain organoids have been used to study the pathogenesis of SARS-CoV-2, human immunodeficiency virus (HIV), HSV-1, and other viral infections of the CNS. In this review, we summarize the advances in the development of viral infection models in brain organoids and their potential application for exploring mechanisms of viral infections of the CNS and in new drug development. The existing limitations are further discussed and the prospects for the development and application of brain organs are prospected.
Highlights
The study of human viral infections is limited by the lack of functional models that simulate normal human physiology and pathophysiology [1]
The findings suggest that microcephaly and other large brain abnormalities in babies born after Zika virus (ZIKV) infection during pregnancy may be just the beginning, there may be a range of neuropsychiatric complications associated with delayed onset [23]
The scientists used human induced pluripotent stem cells to compare patterns of Ab42 accumulation in 2D and 3D neuron cultures infected with HSV-1 [58, 59]. Their in vitro models showed that hiPSC-derived central nervous system (CNS) neurons allowed HSV-1 infection and that 2D neuron cultures showed Ab42 immunoreactivity mainly in HSV-1-infected cells, rarely in uninfected cells or in infected cells that come in contact with antiviral drug
Summary
The study of human viral infections is limited by the lack of functional models that simulate normal human physiology and pathophysiology [1]. Human pathogenic viruses have been studied using immortalized cell lines, primary cells isolated from the body, and a variety of animal hosts [2] These traditional models have made significant progress in helping to understand viral pathogenesis and host pathogen interactions, and have contributed to the development of vaccines and treatment strategies, these models may have limitations in reproducing interactions between pathogens and human hosts [1]. A two-dimensional (2D) research strategy based on induced pluripotent stem cells (iPSC) has provided valuable information for the pathophysiology of neurological diseases, but lacks three-dimensional (3D) properties of their internal structures; tissue structures composed of many different types of cells, and their complex environments and functions cannot be simulated [1, 3, 4]. The development of the human brain presents several unique aspects, such as higher
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