Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques.

Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques.
复制标题

DOI:
10.1038/nm.3362
复制
发表时间:
2013-10
期刊:
影响因子:
82.9
通讯作者:
--
中科院分区:
医学1区
文献类型:
--
作者:

文献摘要

参考文献

被引文献

相似文献

中东呼吸综合征冠状病毒(MERS-CoV)已导致约50%的已知感染者死亡,因此了解其传播机制和发病机制并确定候选治疗方法成为当务之急。Heinz Feldmann、Vincent J. Munster和Michael G. Katze和他们的同事现在报告说,用干扰素-α2b和利巴韦林治疗mers - cov感染的恒河猴可以减少病毒的复制和感染的严重程度,这表明这种组合可能用于感染人类的临床治疗。本文的在线版本(doi:10.1038/nm.3362)包含补充材料,可供授权用户使用。中东呼吸综合征冠状病毒(MERS-CoV)的出现引起了全球关注:该病毒已引起严重呼吸道疾病,截至本文发表时,已有111例确诊病例和52例死亡。治疗干预尚未在体内进行评估;因此,患者管理完全依赖于支持性护理,鉴于高病死率,这种护理不是很有效。恒河猴是已知的中东呼吸综合征冠状病毒感染的唯一模式生物,它会出现急性局部到广泛的肺炎,并伴有短暂的临床疾病,重现轻度至中度的人类中东呼吸综合征冠状病毒病例。干扰素-α2b联合利巴韦林可有效降低MERS-CoV体外复制;因此,我们在恒河猴接种后8小时开始这种治疗。与未经治疗的受感染猕猴相比,接受治疗的动物没有出现呼吸异常,也没有或非常轻微的肺炎放射学证据。此外,治疗动物显示出较低水平的全身(血清)和局部(肺)促炎标志物,以及较少的病毒基因组拷贝,明显的基因表达和较轻的肺部组织病理学变化。综上所述,这些数据表明,用IFN-α2b和利巴韦林治疗MERS-CoV感染的恒河猴可减少病毒复制,调节宿主反应,改善临床结果。由于这两种药物在临床上已经联合用于其他感染,对于MERS-CoV病例的治疗应考虑IFN-α2b和利巴韦林。本文的在线版本(doi:10.1038/nm.3362)包含补充材料,可供授权用户使用。
The Middle East respiratory syndrome coronavirus (MERS-CoV) has killed ∼50% of individuals known to be infected, making understanding its mechanisms of transmission and pathogenesis and identifying candidate treatments a high priority. Heinz Feldmann, Vincent J. Munster and Michael G. Katze and their colleagues now report that treating MERS-CoV-infected rhesus macaques with interferon-α2b and ribavirin reduced virus replication and infection severity, suggesting the potential use of this combination for the clinical treatment of infected humans. The online version of this article (doi:10.1038/nm.3362) contains supplementary material, which is available to authorized users. The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern: the virus has caused severe respiratory illness, with 111 confirmed cases and 52 deaths at the time of this article's publication. Therapeutic interventions have not been evaluated in vivo; thus, patient management relies exclusively on supportive care, which, given the high case-fatality rate, is not highly effective. The rhesus macaque is the only known model organism for MERS-CoV infection, developing an acute localized to widespread pneumonia with transient clinical disease that recapitulates mild to moderate human MERS-CoV cases. The combination of interferon-α2b and ribavirin was effective in reducing MERS-CoV replication in vitro; therefore, we initiated this treatment 8 h after inoculation of rhesus macaques. In contrast to untreated, infected macaques, treated animals did not develop breathing abnormalities and showed no or very mild radiographic evidence of pneumonia. Moreover, treated animals showed lower levels of systemic (serum) and local (lung) proinflammatory markers, in addition to fewer viral genome copies, distinct gene expression and less severe histopathological changes in the lungs. Taken together, these data suggest that treatment of MERS-CoV infected rhesus macaques with IFN-α2b and ribavirin reduces virus replication, moderates the host response and improves clinical outcome. As these two drugs are already used in combination in the clinic for other infections, IFN-α2b and ribavirin should be considered for the management of MERS-CoV cases. The online version of this article (doi:10.1038/nm.3362) contains supplementary material, which is available to authorized users.
DOI: 10.1074/jbc.m806786200
发表时间: 2008-12-26
影响因子: 4.8
作者:
Li, Min;Li, Changgong;Minoo, Parviz
通讯作者: Minoo, Parviz
DOI: 10.1007/s10096-004-1271-9
发表时间: 2005-01
期刊: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
影响因子: --
作者:
Cheng Y;Wong R;Soo YO;Wong WS;Lee CK;Ng MH;Chan P;Wong KC;Leung CB;Cheng G
通讯作者: Cheng G
DOI: 10.1016/j.ajpath.2012.08.019
发表时间: 2012-12-01
影响因子: 6
作者:
Cigna, Natacha;Moshai, Elika Farrokhi;Mailleux, Arnaud A.
通讯作者: Mailleux, Arnaud A.
DOI: 10.1016/s1672-0229(06)60021-1
发表时间: 2006-01-01
影响因子: 9.5
作者:
Noth, Sebastian;Brysbaert, Guillaume;Benecke, Arndt
通讯作者: Benecke, Arndt
DOI: 10.1002/jcb.21142
发表时间: 2007-04-15
影响因子: 4
作者:
Pogach, Melanie S.;Cao, Yuxia;Williams, Mary C.
通讯作者: Williams, Mary C.