Recent advances in unbiased pathogen discovery have implicated astroviruses as pathogens of the central nervous system (CNS) of mammals, including humans. However, the capacity of astroviruses to be cultured in CNS-derived cells in vitro has not been reported to date. Both astrovirus VA1/HMO-C (VA1; mamastrovirus 9) and classic human astrovirus 4 (HAstV4; mamastrovirus 1) have been previously detected from cases of human encephalitis. We tested the ability of primary human neurons, primary human astrocytes, and other immortalized human nervous system cell lines (SK-N-SH, U87 MG, and SW-1088) to support infection and replication of these two astrovirus genotypes. Primary astrocytes and SK-N-SH cells supported the full viral life cycle of VA1 with a >100-fold increase in viral RNA levels during a multistep growth curve, detection of viral capsid, and a >100-fold increase in viral titer. Primary astrocytes were permissive with respect to HAstV4 infection and replication but did not yield infectious virus, suggesting abortive infection. Similarly, abortive infection of VA1 was observed in SW-1088 and U87 MG cells. Elevated expression of the chemokine CXCL10 was detected in VA1-infected primary astrocytes and SK-N-SH cells, suggesting that VA1 infection can induce a proinflammatory host response. These findings establish an in vitro cell culture model that is essential for investigation of the basic biology of astroviruses and their neuropathogenic potential.IMPORTANCE Encephalitis remains a diagnostic conundrum in humans as over 50% of cases are managed without the identification of an etiology. Astroviruses have been detected from the central nervous system of mammals in association with disease, suggesting that this family of RNA viruses could be responsible for cases of some neurological diseases that are currently without an ascribed etiology. However, there are significant barriers to understanding astrovirus infection as the capacity of these viruses to replicate in nervous system cells in vitro has not been determined. We describe primary and immortalized cultured cells of the nervous system that support infection by astroviruses. These results further corroborate the role of astroviruses in causing neurological diseases and will serve as an essential model to interrogate the neuropathogenesis of astrovirus infection.

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星状病毒对神经细胞的体外差异感染。

无偏病原体发现的最新进展表明，星状病毒是包括人类在内的哺乳动物中枢神经系统（CNS）的病原体。然而，迄今尚未报道星形细胞病毒在中枢神经系统来源的细胞中体外培养的能力。先前已从人脑炎病例中检出了星状病毒VA1 / HMO-C（VA1；乳腺病毒9）和经典的人类星状病毒4（HAstV4；乳腺病毒1）。我们测试了主要人类神经元，主要人类星形胶质细胞和其他永生化人类神经系统细胞系（SK-N-SH，U87 MG和SW-1088）支持这两种星状病毒基因型感染和复制的能力。原代星形胶质细胞和SK-N-SH细胞支持VA1的整个病毒生命周期，并在多步生长曲线，病毒衣壳的检测，病毒滴度增加> 100倍。原发性星形胶质细胞允许HAstV4感染和复制，但不产生感染性病毒，提示流产感染。同样，在SW-1088和U87 MG细胞中也观察到VA1的流产感染。在感染VA1的原代星形胶质细胞和SK-N-SH细胞中检测到趋化因子CXCL10的表达升高，表明VA1感染可诱导促炎性宿主反应。这些发现建立了一个体外细胞培养模型，该模型对于研究星状病毒的基本生物学及其神经致病性潜力至关重要。重要信息脑炎仍然是人类的诊断难题，因为超过50％的病例在未确定病因的情况下得到管理。已经从哺乳动物的中枢神经系统中发现了与疾病相关的星状病毒，这表明该RNA病毒家族可能是造成某些目前尚无病因的神经系统疾病的原因。但是，了解星状病毒感染存在很大的障碍，因为尚未确定这些病毒在体外神经系统细胞中复制的能力。我们描述了支持星状病毒感染的神经系统原代和永生培养细胞。这些结果进一步证实了星状病毒在引起神经系统疾病中的作用，并将成为询问星状病毒感染的神经病学的基本模型。提示该RNA病毒家族可能与目前尚无病因的某些神经系统疾病有关。但是，了解星状病毒感染存在很大的障碍，因为尚未确定这些病毒在体外神经系统细胞中复制的能力。我们描述了支持星状病毒感染的神经系统原代和永生培养细胞。这些结果进一步证实了星状病毒在引起神经系统疾病中的作用，并将成为询问星状病毒感染的神经病学的基本模型。提示该RNA病毒家族可能与目前尚无病因的某些神经系统疾病有关。但是，了解星状病毒感染存在很大的障碍，因为尚未确定这些病毒在体外神经系统细胞中复制的能力。我们描述了支持星状病毒感染的神经系统原代和永生培养细胞。这些结果进一步证实了星状病毒在引起神经系统疾病中的作用，并将成为询问星状病毒感染的神经病学的基本模型。由于尚未确定这些病毒在体外神经系统细胞中复制的能力，因此了解星状病毒感染存在很大障碍。我们描述了支持星状病毒感染的神经系统原代和永生培养的细胞。这些结果进一步证实了星状病毒在引起神经系统疾病中的作用，并将成为询问星状病毒感染的神经病学的基本模型。由于尚未确定这些病毒在体外神经系统细胞中复制的能力，因此了解星状病毒感染存在很大障碍。我们描述了支持星状病毒感染的神经系统原代和永生培养细胞。这些结果进一步证实了星状病毒在引起神经系统疾病中的作用，并将成为询问星状病毒感染的神经病学的基本模型。