未经证实:呼吸道合胞病毒(RSV)是抗病毒干扰素(IFN)反应的弱诱导剂,导致免疫不完全和RSV疾病。几种RSV蛋白改变抗病毒反应,包括非结构蛋白(NS1,NS2)和主要的病毒表面蛋白,也就是说,融合(F)和附着(G)蛋白。G蛋白部分通过CX3C趋化因子基序修饰宿主对感染的免疫应答。抗G蛋白单克隆抗体(mAb),也就是说,靶向G蛋白CX3C趋化因子基序的克隆3D3和2D10可中和RSV并抑制G蛋白-CX3CR1介导的趋化性。
未经证实:确定抗RSVF和G蛋白的单克隆抗体如何修饰对RSV感染的I型和III型IFN应答。
未经证实:由于G蛋白CX3C基序与IFN拮抗有关,我们评估了两种阻断G蛋白CX3C-CX3CR1相互作用的mAb,并使用功能细胞试验和小鼠模型比较了与同种型mAb对照的应答.
未授权:在预防性mAb处理后,用RSVLine19F感染小鼠肺上皮细胞(MLE-15细胞)和BALB/c小鼠。测定细胞上清液或支气管肺泡灌洗液(BALF)的I型和III型IFN。询问细胞IFN相关基因表达的变化。
UNASSIGNED:与RSV感染后的同种型对照相比,用抗G蛋白mAb(3D3)治疗可改善IFN应答,部分独立于中和,这与上调的SOCS1表达有关。
UNASSIGNED:这些研究结果表明,抗G蛋白抗体改善了保护性早期抗病毒反应,这对疫苗和治疗设计具有重要意义。
UNASSIGNED:RSV是婴儿和老年人呼吸系统疾病的主要原因。唯一食品和药物管理局批准的预防性治疗仅限于抗F蛋白单克隆抗体(mAb),也就是说,帕利珠单抗对RSV疾病具有中等疗效。越来越多的证据表明,靶向RSV附着(G)蛋白可以提供对RSV疾病的改善的保护。已知G蛋白是IFN拮抗剂,和IFN已被证明对RSV疾病有保护作用。在这项研究中,我们比较了小鼠肺上皮(MLE-15)细胞和用抗G蛋白或抗F蛋白mAb治疗的RSVLine19F感染小鼠的IFN应答。测定I型和III型IFN的水平。与同种型处理的对照相比,抗G蛋白mAb改善了IFN的水平。这些发现支持抗G蛋白mAb介导改善的IFN对RSV疾病的应答的概念。这可以改善RSV感染的治疗。
UNASSIGNED: Respiratory syncytial virus (RSV) is a poor inducer of antiviral interferon (IFN) responses which result in incomplete immunity and RSV disease. Several RSV proteins alter antiviral responses, including the non-structural proteins (NS1, NS2) and the major viral surface proteins, that is, fusion (F) and attachment (G) proteins. The G protein modifies the host immune response to infection linked in part through a CX3 C chemokine motif. Anti-G protein monoclonal antibodies (mAbs), that is, clones 3D3 and 2D10 that target the G protein CX3C chemokine motif can neutralize RSV and inhibit G protein-CX3CR1 mediated chemotaxis.
UNASSIGNED: Determine how monoclonal antibodies against the RSV F and G proteins modify the type I and III IFN responses to RSV infection.
UNASSIGNED: As the G protein CX3 C motif is implicated in IFN antagonism, we evaluated two mAbs that block G protein CX3C-CX3CR1 interaction and compared responses to isotype mAb control using a functional cellular assay and mouse model.
UNASSIGNED: Mouse lung epithelial cells (MLE-15 cells) and BALB/c mice were infected with RSV Line19 F following prophylactic mAb treatment. Cell supernatant or bronchoalveolar lavage fluid (BALF) were assayed for types I and III IFNs. Cells were interrogated for changes in IFN-related gene expression.
UNASSIGNED: Treatment with an anti-G protein mAb (3D3) resulted in improved IFN responses compared with isotype control following infection with RSV, partially independently of neutralization, and this was linked to upregulated SOCS1 expression.
UNASSIGNED: These findings show that anti-G protein antibodies improve the protective early antiviral response, which has important implications for vaccine and therapeutic design.
UNASSIGNED: RSV is a leading cause of respiratory disease in infants and the elderly. The only Food and Drug Administration-approved prophylactic treatment is limited to an anti-F protein monoclonal antibody (mAb), that is, palivizumab which has modest efficacy against RSV disease. Accumulating evidence suggests that targeting the RSV attachment (G) protein may provide improved protection from RSV disease. It is known that the G protein is an IFN antagonist, and IFN has been shown to be protective against RSV disease. In this study, we compared IFN responses in mouse lung epithelial (MLE-15) cells and in mice infected with RSV Line19 F treated with anti-G protein or anti-F protein mAbs. The levels of type I and III IFNs were determined. Anti-G protein mAbs improved the levels of IFNs compared with isotype-treated controls. These findings support the concept that anti-G protein mAbs mediate improved IFN responses against RSV disease, which may enable improved treatment of RSV infections.