Murine interferon lambdas (type III interferons) exhibit potent antiviral activity in vivo in a poxvirus infection model
Murine interferon lambdas (type III interferons) exhibit potent antiviral activity in vivo in a poxvirus infection model
复制标题
DOI：
10.1099/vir.0.80904-0
复制
发表时间：
2005-06-01
影响因子：
3.8
通讯作者：
Smith, GL
中科院分区：
文献类型：
--
作者：
Bartlett, NW;Buttigieg, K;Smith, GL
人干扰素(干扰素-波长S)(III型IFN)通过与I型和II型IFN所使用的受体复合体结合，随后通过Janus激酶信号转导和转录激活因子(STAT)途径传递信号，在体外显示出抗病毒活性。然而，缺乏III型干扰素在体内病毒感染过程中发挥作用的证据。本文报道了用重组痘苗病毒表达小鼠干扰素-λS，并证明这些蛋白在体内具有很强的抗病毒活性。表达小鼠干扰素-lambda 2(v干扰素-lambda 2)和干扰素-lambda 3(vIFN-lambda 3)的VACV在组织培养中显示正常生长，并在感染细胞提取液和培养上清液中表达N-糖基化的干扰素-lambda，在两种不同的小鼠模型上观察了小鼠干扰素-lambda S在病毒感染过程中的作用。与对照病毒相比，vIFN-lambda 2和vIFN-lambda 3对鼻腔感染的小鼠是无毒的，并且没有引起疾病或体重减轻的迹象。肺泡灌洗液中的淋巴细胞和全肺淋巴细胞制剂中的CD4(+)T细胞的增加与vIFN-lambda 2的减弱有关。此外，vIFN-lambda 2可以更快地从感染的肺部清除，与对照病毒相比，它不会传播到大脑。在皮内感染模型中，干扰素-lambda 2的表达也可以减轻VACV，其特征是延迟病变发生和缩小病变大小。因此，通过在小鼠感染模型中表征小鼠干扰素-波长S，已经证明了干扰素-波长S在应答痘病毒感染时的强大的抗病毒和免疫刺激活性。
Human interferon lambdas (IFN-lambda s) (type III IFNs) exhibit antiviral activity in vitro by binding to a receptor complex distinct from that used by type I and type II IFNs, and subsequent signalling through the Janus kinase signal transducers and activators of transcription (STAT) pathway. However, evidence for a function of type III IFNs during virus infection in vivo is lacking. Here, the expression of murine IFN-lambda s by recombinant vaccinia virus (VACV) is described and these proteins are shown to have potent antiviral activity in vivo. VACV expressing murine IFN-lambda 2 (vIFN-lambda 2) and IFN-lambda 3 (vIFN-lambda 3) showed normal growth in tissue culture and expressed N-glycosylated IFN-lambda in infected cell extracts and culture supernatants, The role that murine IFN-lambda s play during virus infection was assessed in two different mouse models. vIFN-lambda 2 and vIFN-lambda 3 were avirulent for mice infected intranasally and induced no signs of illness or weight loss, in contrast to control viruses. Attenuation of vIFN-lambda 2 was associated with increases in lymphocytes in bronchial alveolar lavages and CD4(+) T cells in total-lung lymphocyte preparations. In addition, vIFN-lambda 2 was cleared more rapidly from infected lungs and, in contrast to control viruses, did not disseminate to the brain. Expression of IFN-lambda 2 also attenuated VACV in an intradermal-infection model, characterized by a delay in lesion onset and reduced lesion size. Thus, by characterizing murine IFN-lambda s within a mouse infection model, the potent antiviral and immunostimulatory activity of IFN-lambda s in response to poxvirus infection has been demonstrated.