Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures.
Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures.
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DOI：
10.3390/v13010091
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发表时间：
2021-01-11
期刊：
影响因子：
--
通讯作者：
Kohl A
中科院分区：
文献类型：
--
作者：
Schultz V;Cumberworth SL;Gu Q;Johnson N;Donald CL;McCanney GA;Barrie JA;Da Silva Filipe A;Linington C;Willison HJ;Edgar JM;Barnett SC;Kohl A
了解寨卡病毒（黄病毒科; ZIKV）如何影响神经细胞对于理解与感染相关的病理至关重要。虽然ZIKV在神经发育中的作用已被充分记录，但对成人神经系统的影响仍然不清楚。在这里，我们研究了ZIKV感染在已建立的成熟有髓鞘中枢神经系统（CNS）培养物中的作用。感染导致有髓纤维损伤，当首次检测到髓鞘损伤以及轴突病理学时出现ZIKV阳性细胞，表明后者是少突胶质细胞感染的结果。转录组分析揭示了在ZIKV感染期间上调的宿主因子。一种这样的因子，CCL 5，在体外被验证为抑制髓鞘形成。从感染的文化转移UV灭活媒体没有损害髓鞘和轴突，这表明病毒复制是必要的，以诱导观察到的效果。这些数据表明，ZIKV感染影响CNS细胞，即使在髓鞘形成之后-这对跳跃式传导和神经元功能至关重要-已经发生。了解该病毒在各个发育阶段（包括成熟的中枢神经系统）的靶点，以及细胞类型感染的后续影响，对于了解治疗干预的有效时间范围是必要的。
Understanding how Zika virus (Flaviviridae; ZIKV) affects neural cells is paramount in comprehending pathologies associated with infection. Whilst the effects of ZIKV in neural development are well documented, impact on the adult nervous system remains obscure. Here, we investigated the effects of ZIKV infection in established mature myelinated central nervous system (CNS) cultures. Infection incurred damage to myelinated fibers, with ZIKV-positive cells appearing when myelin damage was first detected as well as axonal pathology, suggesting the latter was a consequence of oligodendroglia infection. Transcriptome analysis revealed host factors that were upregulated during ZIKV infection. One such factor, CCL5, was validated in vitro as inhibiting myelination. Transferred UV-inactivated media from infected cultures did not damage myelin and axons, suggesting that viral replication is necessary to induce the observed effects. These data show that ZIKV infection affects CNS cells even after myelination—which is critical for saltatory conduction and neuronal function—has taken place. Understanding the targets of this virus across developmental stages including the mature CNS, and the subsequent effects of infection of cell types, is necessary to understand effective time frames for therapeutic intervention.
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影响因子：
39.2
作者：
Costa F;Sarno M;Khouri R;de Paula Freitas B;Siqueira I;Ribeiro GS;Ribeiro HC;Campos GS;Alcântara LC;Reis MG;Weaver SC;Vasilakis N;Ko AI;Almeida AR
通讯作者：
Almeida AR
影响因子：
14.9
作者：
Babicki S;Arndt D;Marcu A;Liang Y;Grant JR;Maciejewski A;Wishart DS
通讯作者：
Wishart DS
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
29
作者：
Ferreira da Silva, Ivan Rocha;Frontera, Jennifer A.;Moreira do Nascimento, Osvaldo Jose
通讯作者：
Moreira do Nascimento, Osvaldo Jose
影响因子：
7.1
作者：
Cumberworth SL;Barrie JA;Cunningham ME;de Figueiredo DPG;Schultz V;Wilder-Smith AJ;Brennan B;Pena LJ;Freitas de Oliveira França R;Linington C;Barnett SC;Willison HJ;Kohl A;Edgar JM
通讯作者：
Edgar JM