Distinct Antiviral Roles for Human 2′,5′-Oligoadenylate Synthetase Family Members against Dengue Virus Infection
Distinct Antiviral Roles for Human 2′,5′-Oligoadenylate Synthetase Family Members against Dengue Virus Infection
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DOI：
10.4049/jimmunol.0902728
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发表时间：
2009-12-15
影响因子：
4.4
通讯作者：
Lin, Yi-Ling
中科院分区：
文献类型：
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作者：
Lin, Ren-Jye;Yu, Han-Pang;Lin, Yi-Ling
寡腺苷酸合成酶（OAS）及其下游效应子RNase 1在宿主防御病毒感染中起重要作用。Oas 1b是小鼠基因组中8个Oas 1基因之一，已被鉴定为小鼠黄病毒抗性基因。在人类OAS基因家族中已鉴定出OAS 1、OAS 2、OAS 3和OAS样（OASL）四种基因，并且通过选择性剪接可产生10种同种型，包括OAS 1（p42、p44、p46、p48和p52）、OAS 2（p69和p71）、OAS 3（p100）和OASL（p30和p59）。在这项研究中，我们确定了人类OAS/RNase L途径在宿主防御登革病毒（DEN）感染中的作用，并评估了人类OAS家族中每种亚型的抗病毒潜力。DEN复制减少过表达和增强敲低RNase L的表达，表明RNase L对DEN复制在人类细胞中的保护作用。人OAS 1 p42、OAS 1 p46和OAS 3 p100通过RNase L依赖性机制阻断DEN复制，但其他OAS亚型不阻断。此外，这三种OAS异构体的抗DEN活性与它们在DEN感染的细胞中触发RNase L活化的能力相关。因此，OAS 1 p42/p46和OAS 3 p100可能有助于宿主防御DEN感染，并在决定DEN疾病严重程度的结果中发挥作用。免疫学杂志，2009，183：8035-8043.
The 2',5'-oligoadenylate synthetase (OAS) and its downstream effector RNase 1, play important roles in host defense against virus infection. Oas1b, one of the eight Oas1 genes in the mouse genome, has been identified as a murine flavivirus-resistance gene. Four genes, OAS1, OAS2, OAS3, and OAS-like (OASL), have been identified in the human OAS gene family, and 10 isoforms, including OAS1 (p42, p44, p46, p48, and p52), OAS2 (p69 and p71), OAS3 (p100), and OASL (p30 and p59) can be generated by alternative splicing. In this study, we determined the role of the human OAS/RNase L pathway in host defense against dengue virus (DEN) infection and assessed the antiviral potential of each isoform in the human OAS family. DEN replication was reduced by overexpression and enhanced by knockdown of RNase L expression, indicating a protective role for RNase L against DEN replication in human cells. The human OAS1 p42, OAS1 p46, and OAS3 p100, but not the other OAS isoforms, blocked DEN replication via an RNase L-dependent mechanism. Furthermore, the anti-DEN activities of these three OAS isoforms correlated with their ability to trigger RNase L activation in DEN-infected cells. Thus, OAS1 p42/p46 and OAS3 p 100 are likely to contribute to host defense against DEN infection and play a role in determining the outcomes of DEN disease severity. The Journal of Immunology, 2009, 183: 8035-8043.