Bourne Nigel, Scholle Frank, Silva Maria Carlan, Rossi Shannan L, Dewsbury Nathan, Judy Barbara, De Aguiar Juliana B, Leon Megan A, Estes D Mark, Fayzulin Rafik, Mason Peter W
Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555-0436, USA.
J Virol. 2007 Sep;81(17):9100-8. doi: 10.1128/JVI.00316-07. Epub 2007 Jun 13.
Infection of cells with flaviviruses in vitro is reduced by pretreatment with small amounts of type I interferon (IFN-alpha/beta). Similarly, pretreatment of animals with IFN and experiments using mice defective in IFN signaling have indicated a role for IFN in controlling flavivirus disease in vivo. These data, along with findings that flavivirus-infected cells block IFN signaling, suggest that flavivirus infection can trigger an IFN response. To investigate IFN gene induction by the very first cells infected during in vivo infection with the flavivirus West Nile virus (WNV), we infected mice with high-titer preparations of WNV virus-like particles (VLPs), which initiate viral genome replication in cells but fail to spread. These studies demonstrated a brisk production of IFN in vivo, with peak levels of over 1,000 units/ml detected in sera between 8 and 24 h after inoculation by either the intraperitoneal or footpad route. The IFN response was dependent on genome replication, and WNV genomes and WNV antigen-positive cells were readily detected in the popliteal lymph nodes (pLN) of VLP-inoculated mice. High levels of IFN mRNA transcripts and functional IFN were also produced in VLP-inoculated IFN regulatory factor 3 null (IRF3(-/-)) mice, indicating that IFN production was independent of the IRF3 pathways to IFN gene transcription, consistent with the IFN type produced (predominantly alpha).
用少量I型干扰素（IFN-α/β）预处理可降低黄病毒在体外对细胞的感染。同样，用IFN对动物进行预处理以及使用IFN信号缺陷小鼠进行的实验表明，IFN在体内控制黄病毒疾病中发挥作用。这些数据，连同黄病毒感染细胞会阻断IFN信号的研究结果，表明黄病毒感染可触发IFN反应。为了研究在西尼罗河病毒（WNV）体内感染过程中最早被感染的细胞对IFN基因的诱导作用，我们用高滴度的WNV病毒样颗粒（VLP）制剂感染小鼠，这些颗粒可在细胞中启动病毒基因组复制，但无法传播。这些研究表明，体内可快速产生IFN，通过腹腔内或足垫途径接种后，在8至24小时之间，血清中检测到的IFN峰值水平超过1000单位/毫升。IFN反应依赖于基因组复制，并且在接种VLP的小鼠的腘淋巴结（pLN）中很容易检测到WNV基因组和WNV抗原阳性细胞。在接种VLP的IFN调节因子3缺失（IRF3（-/-））小鼠中也产生了高水平的IFN mRNA转录本和功能性IFN，这表明IFN的产生独立于IFN基因转录的IRF3途径，这与所产生的IFN类型（主要是α）一致。
