A Respiratory Syncytial Virus (RSV) Anti-G Protein F(ab′)2 Monoclonal Antibody Suppresses Mucous Production and Breathing Effort in RSV rA2-line19F-Infected BALB/c Mice

A Respiratory Syncytial Virus (RSV) Anti-G Protein F(ab′)2 Monoclonal Antibody Suppresses Mucous Production and Breathing Effort in RSV rA2-line19F-Infected BALB/c Mice
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DOI:
10.1128/jvi.01164-13
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发表时间:
2013-10-01
影响因子:
5.4
通讯作者:
Anderson, Larry J.
Anderson, Larry J.
中科院分区:
医学2区
文献类型:
--
作者:
Boyoglu-Barnum, Seyhan;Gaston, Kelsey A.;Anderson, Larry J.

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呼吸道合胞病毒(RSV)属于副粘病毒科,是幼儿严重下呼吸道感染的唯一最重要原因,但没有高效的治疗方法或疫苗。气道阻力增加和气道粘蛋白产生增加是儿童RSV感染的两种表现。RSV rA 2-line 19 F感染诱导BALB/c小鼠肺粘液产生和呼吸努力增加,并提供了一种在动物模型中评估RSV疾病这些表现的方法。在本研究中,我们研究了用抗G蛋白单克隆抗体(MAb)131-2G的F(ab ')(2)形式预防性治疗对RSV rA 2-line 19 F攻击小鼠疾病的影响。F(ab ')(2)131-2G不影响病毒复制。它和减少病毒复制的完整形式防止了呼吸努力和气道粘蛋白产生的增加,以及体重减轻,肺部炎症细胞浸润和肺部P物质和肺部Th 2细胞因子水平,这些都发生在用这种病毒攻击的小鼠中。这些数据表明RSV G蛋白导致RSV疾病的突出表现,并且MAb 131-2G可以预防RSV疾病的这些表现而不抑制病毒感染。
Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. Increased airway resistance and increased airway mucin production are two manifestations of RSV infection in children. RSV rA2-line19F infection induces pulmonary mucous production and increased breathing effort in BALB/c mice and provides a way to assess these manifestations of RSV disease in an animal model. In the present study, we investigated the effect of prophylactic treatment with the F(ab')(2) form of the anti-G protein monoclonal antibody (MAb) 131-2G on disease in RSV rA2-line19F-challenged mice. F(ab')(2) 131-2G does not affect virus replication. It and the intact form that does decrease virus replication prevented increased breathing effort and airway mucin production, as well as weight loss, pulmonary inflammatory-cell infiltration, and the pulmonary substance P and pulmonary Th2 cytokine levels that occur in mice challenged with this virus. These data suggest that the RSV G protein contributes to prominent manifestations of RSV disease and that MAb 131-2G can prevent these manifestations of RSV disease without inhibiting virus infection.