Sarkis Sarkis, Dabo Stéphanie, Lise Marie-Claude, Neuveut Christine, Meurs Eliane F, Lacoste Vincent, Lavergne Anne
Laboratoire des Interactions Virus-Hôtes, Institut Pasteur de la Guyane, Cayenne, French Guiana.
Hepacivirus and Innate Immunity, Institut Pasteur, 75015 Paris, France.
Dev Comp Immunol. 2018 Aug;85:95-107. doi: 10.1016/j.dci.2018.04.006. Epub 2018 Apr 7.
Bats are known to harbor many zoonotic viruses, some of which are pathogenic to other mammals while they seem to be harmless in bats. As the interferon (IFN) response represents the first line of defense against viral infections in mammals, it is hypothesized that activation of the IFN system is one of the mechanisms enabling bats to co-exist with viruses. We have previously reported induction of type I IFN in a cell line from the common vampire bat, Desmodus rotundus, upon polyinosinic:polycytidylic acid (poly(I:C)) stimulation. To deepen our knowledge on D. rotundus' IFN-I antiviral response, we molecularly characterized three interferon-stimulated genes (ISGs), OAS1, PKR and ADAR1, closely implicated in the IFN-I antiviral response, and tested their functionality in our cellular model. We first found that D. rotundus encoded two OAS1 paralogs, OAS1a and OAS1b, and that the functional domains of the four ISGs characterized were highly conserved with those of other mammals. Despite their significant transcription level in the absence of stimulation, the transcription of the four ISGs characterized was enhanced by poly(I:C). In addition, the transcription of OAS1a and OAS1b appears to be differentially regulated. These findings demonstrate an active ISG antiviral response in D. rotundus in which OAS1b may play an important role.
众所周知,蝙蝠携带多种人畜共患病毒,其中一些病毒对其他哺乳动物具有致病性,但在蝙蝠体内似乎无害。由于干扰素(IFN)反应是哺乳动物抵御病毒感染的第一道防线,因此有人推测,激活IFN系统是蝙蝠与病毒共存的机制之一。我们之前报道过,在多聚肌苷酸:多聚胞苷酸(poly(I:C))刺激下,普通吸血蝙蝠(Desmodus rotundus)的细胞系中会诱导产生I型干扰素。为了深入了解普通吸血蝙蝠的I型干扰素抗病毒反应,我们对三个与I型干扰素抗病毒反应密切相关的干扰素刺激基因(ISG),即2'-5'-寡腺苷酸合成酶1(OAS1)、蛋白激酶R(PKR)和腺苷脱氨酶1(ADAR1)进行了分子特征分析,并在我们的细胞模型中测试了它们的功能。我们首先发现普通吸血蝙蝠编码了两个OAS1旁系同源基因,即OAS1a和OAS1b,并且所分析的四个ISG的功能域与其他哺乳动物的功能域高度保守。尽管在未受刺激的情况下这四个ISG具有显著的转录水平,但poly(I:C)会增强它们的转录。此外,OAS1a和OAS1b的转录似乎受到不同的调控。这些发现表明普通吸血蝙蝠中存在活跃的ISG抗病毒反应,其中OAS1b可能起重要作用。