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Cell Reports:抗真菌药可能增加流感易感性

2013-11-26 王英 生物通

美国马萨诸塞大学医学院和英国桑格研究所的科学家们发现,一种常用的抗真菌药物,能够增加小鼠和细胞培养物对流感感染的易感性。发表在11月21日CellReports杂志上的这项研究表明,常用在癌症和骨髓移植患者中对抗侵入性真菌感染的两性霉素B,能够使一种重要的抗病毒蛋白失效,使病毒更容易感染细胞。接受抗真菌治疗的患者,可能会出现功能性免疫功能不全,更容易感染流感和潜在的其它病毒。 在11月2

美国马萨诸塞大学医学院和英国桑格研究所的科学家们发现,一种常用的抗真菌药物,能够增加小鼠和细胞培养物对流感感染的易感性。发表在11月21日Cell Reports杂志上的这项研究表明,常用在癌症骨髓移植患者中对抗侵入性真菌感染的两性霉素B,能够使一种重要的抗病毒蛋白失效,使病毒更容易感染细胞。接受抗真菌治疗的患者,可能会出现功能性免疫功能不全,更容易感染流感和潜在的其它病毒。【原文下载】

在11月21日的Cell Reports杂志上发表的一项研究中,来自美国马萨诸塞大学医学院(UMMS)和英国威康信托基金会桑格研究所的科学家们发现,一种常用的抗真菌药物,能够增加小鼠和细胞培养物对流感感染的易感性。他们发现,常用在癌症和骨髓移植患者中对抗侵入性真菌感染的两性霉素B,能够使一种重要的抗病毒蛋白失效,使病毒更容易感染细胞。接受抗真菌治疗的患者,可能会出现功能性免疫功能不全,更容易感染流感和潜在的其它病毒。

本研究的高级作者、微生物&生理学系统助理教授Abraham Brass博士说:“然而,这些研究不能确定这种相互作用能转化为患者的临床指导意义,这表明一些警惕是必要的,尤其是对正在接受癌症治疗和可能已经有了免疫系统抑制的患者来说。”


本研究的共同作者、桑格研究所的教授Paul Kellam博士说:“这是一个重要的发现,现在应该调查接受某种抗真菌治疗的患者的治疗后果。当这些患者处于流感感染风险时,应当向他们提供预防性的流感疫苗、快速的抗病毒治疗或者选择性的抗真菌治疗。”

在几乎所有人细胞中发现的干扰素诱导跨膜蛋白3(IFITM3)能够改变细胞膜,使病毒——例如流感病毒——更难穿透细胞的外层。当IFITM3不活跃时,流感病毒可能更轻而易举地浸润和感染细胞。Kellam博士和同事们以前进行的研究也表明,具有IFITM3基因遗传变异的人,更容易感染流感。

当Brass和他的研究团队发现两性霉素B和流感之间关系的时候,他们正在设法理解IFITM3是如何保护细胞不受病毒感染的。Brass说:“实验室的几个细胞培养物遭受一种真菌的污染,我们用两性霉素B治疗它们,但并不知道这种药物对IFITM3活动有影响。令人惊讶的是,当我们检测流感感染时,我们在正常的野生型细胞中没有发现IFITM3活动。在那时,我们开始怀疑两性霉素B对IFITM3有影响。”

这个出乎意料的真相开辟了一项新的调查研究,结果表明,两性霉素B妨碍IFITM3避开流感病毒。本研究的共同第一作者、Brass实验室的助理研究员ChristopherR.Chin说:“当我们用抗真菌药物治疗肺癌细胞时,我们发现,抗病毒保护一般出现在IFITM3消失后。”

为了更好地理解两性霉素B对IFITM3的影响,Brass与Kellam合作,用抗真菌药物治疗小鼠。他们发现,一旦小鼠得了流感,它们表现出与完全缺乏保护性IFITM3基因的小鼠相同的、更严重的流感症状。当流感病毒缺乏时,两性霉素B治疗的小鼠显示无生病迹象。

这项研究表明,接受两性霉素B抗真菌治疗的患者可能会潜在地丢失IFITM3的保护作用,使免疫系统已经缺乏抵抗力的患者感染流感的风险增加。

Brass说:“有时候,一种非常有用的药物可能也具有一个不可预见的效果。我们现在发现,细胞和小鼠中的两性霉素B使身体防御流感病毒的绝大部分自然能力丧失。我们希望,对这个相互作用的影响后果的报道,能够激励进一步的转化研究和潜在地指导患者护理。”

Kellam和Brass一致认为,还需要进一步的研究工作,来评估是否这个效果对接受以两性霉素B为基础的治疗的患者具有临床意义。

原文出处:

Tsai-Yu Lin, Christopher R.Chin, Aaron R.Everitt,Simon Clare, Jill M.Perreira,George Savidis,Aaron M.Aker, Sinu P.John, David Sarlah, Erick M.Carreira, Stephen J.Elledge, Paul Kellam, Abraham L.Brasss.Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-Mediated Restriction.Cell Reports, 21 November 2013.【原文下载】


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    2014-06-11 维他命
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    2014-05-31 amy0563
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    2013-11-28 zhaojie88
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