![]() Recent advances in stem cell biology have made it possible to grow organoids in vitro, mimicking a variety of human tissues, including the brain, lungs, and intestines ( 2).Ī growing body of clinical data suggests that many pathogen infections eventually lead to a range of brain diseases. Organoids are derived from human stem cells and retain the genomic background, cellular organization, and function of their tissues of origin. Although the 3D-based organoid culture research strategy is still in its infancy, it has provided a new method for modeling human disease ( Table 1 ) ( 4). 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 thus, tissue structures composed of many different types of cells, and their complex environments and functions cannot be simulated ( 1, 3, 4). Recently developed humanized mouse models are more valuable for human viral disease research, but they are expensive and difficult to maintain ( 3). Although 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). For decades, human pathogenic viruses have been studied using immortalized cell lines, primary cells isolated from the body, and a variety of animal hosts ( 2). The study of human viral infections is limited by the lack of functional models that simulate normal human physiology and pathophysiology ( 1). The existing limitations are further discussed and the prospects for the development and application of brain organs are prospected. 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. 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. Modeling Zika virus (ZIKV) infection in brain organoids may help elucidate the relationship between ZIKV infection and microcephaly. 4Department of Microbiology and Immunology, Kunming Medical University, Kunming, Chinaīrain organoids, or brainoids, have shown great promise in the study of central nervous system (CNS) infection.3Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming, China.2Department of Pediatrics, The Affiliated Children Hospital, Kunming Medical University, Kunming, China.1Yunnan Province Key Laboratory for Tropical Infectious Diseases in Universities, Kunming Medical University, Kunming, China.Xuan Su 1,2 Peng Yue 1,3 Jing Kong 1,3 Xin Xu 1,4 Yu Zhang 1,4 Wenjing Cao 1,3 Yuxin Fan 1,4 Meixiao Liu 1,4 Jingjing Chen 1,3 Aihua Liu 1,3* Fukai Bao 1,4*
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