Differential pathogenesis of Usutu virus isolates in mice.

Differential pathogenesis of Usutu virus isolates in mice.
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DOI:
10.1371/journal.pntd.0008765
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发表时间:
2020-10
影响因子:
3.8
通讯作者:
Duggal NK
Duggal NK
中科院分区:
医学2区
文献类型:
--
作者:
Kuchinsky SC;Hawks SA;Mossel EC;Coutermarsh-Ott S;Duggal NK

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乌苏图病毒(USUV;黄病毒)是西尼罗河病毒的系统发育和生态近亲,是一种人畜共患病毒,可引起人类神经侵袭性疾病。 USUV 维持在库蚊和鸟类之间的地方性动物循环中。自 1959 年在南非首次隔离以来,USUV 已遍布非洲和欧洲。过去几十年来,报告的人类病例有所增加,主要是在欧洲,症状从轻度发热性疾病到严重的神经系统影响不等。在这项研究中,我们调查了 USUV 在欧洲出现期间是否变得更具致病性。干扰素 α/β 受体敲除 (Ifnar1-/-) 小鼠接种了来自非洲和欧洲的最新 USUV 菌株,以及历史悠久的 1959 年南非菌株。三种测试的非洲菌株和一种来自西班牙的欧洲菌株导致接种小鼠 100% 死亡,且存活时间和组织病理学相似。出乎意料的是,与接种其他菌株的小鼠相比,来自荷兰的欧洲菌株仅导致 12% 的死亡率,并且小鼠组织中的组织病理学显着减少。接种最新非洲毒株的小鼠病毒血症最高,接种荷兰毒株的小鼠病毒血症最低。根据系统发育学,来自西班牙和荷兰的 USUV 分离株是分别引入欧洲的,这表明欧洲流行的 USUV 菌株的疾病结果可能有所不同。这些结果还表明,虽然最近欧洲报告了更多的人类 USUV 疾病病例,但非洲流行的 USUV 毒株仍然是潜在的主要健康问题。乌苏图病毒(USUV)是一种新兴的蚊媒病毒,可导致人类严重的神经侵袭性疾病。 USUV于1959年首次在非洲发现,近年来人类患病病例有所增加。目前,大多数 USUV 疾病病例都报告在该病毒目前正在传播的欧洲。病例数量增加的一种可能性是,USUV 毒株在从非洲传播到欧洲的过程中,随着时间的推移,致病性变得更强。我们在小鼠模型中比较了来自非洲和欧洲的五种 USUV 分离株的发病机制。三种来自非洲的分离株和一种来自欧洲的分离株导致小鼠 100% 死亡。令人惊讶的是,来自荷兰的一种分离株仅导致 12% 的死亡率。与接种其他四种菌株的小鼠相比,接种荷兰菌株的小鼠组织中观察到的组织病理学明显较少。我们的研究结果表明,尽管最近欧洲报告了更多的人类 USUV 疾病病例,但非洲 USUV 菌株也具有高致病性。
Usutu virus (USUV; Flavivirus), a close phylogenetic and ecological relative of West Nile virus, is a zoonotic virus that can cause neuroinvasive disease in humans. USUV is maintained in an enzootic cycle between Culex mosquitoes and birds. Since the first isolation in 1959 in South Africa, USUV has spread throughout Africa and Europe. Reported human cases have increased over the last few decades, primarily in Europe, with symptoms ranging from mild febrile illness to severe neurological effects. In this study, we investigated whether USUV has become more pathogenic during emergence in Europe. Interferon α/β receptor knockout (Ifnar1-/-) mice were inoculated with recent USUV isolates from Africa and Europe, as well as the historic 1959 South African strain. The three tested African strains and one European strain from Spain caused 100% mortality in inoculated mice, with similar survival times and histopathology in tissues. Unexpectedly, a European strain from the Netherlands caused only 12% mortality and significantly less histopathology in tissues from mice compared to mice inoculated with the other strains. Viremia was highest in mice inoculated with the recent African strains and lowest in mice inoculated with the Netherlands strain. Based on phylogenetics, the USUV isolates from Spain and the Netherlands were derived from separate introductions into Europe, suggesting that disease outcomes may differ for USUV strains circulating in Europe. These results also suggest that while more human USUV disease cases have been reported in Europe recently, circulating African USUV strains are still a potential major health concern. Usutu virus (USUV) is an emerging mosquito-borne virus that causes severe neuroinvasive disease in humans. USUV was first detected in Africa in 1959, and cases of human disease have increased in recent years. Most USUV disease cases are now reported in Europe, where the virus currently circulating. One possibility for the increase in case numbers is that USUV strains have become more pathogenic over time during its spread from Africa into Europe. We compared the pathogenesis of five USUV isolates from Africa and Europe in a mouse model. Three isolates from Africa and one isolate from Europe caused 100% mortality in mice. Surprisingly, one isolate from Netherlands caused only 12% motality. Significantly less histopathology was observed in tissues from mice inoculated with the Netherlands strain compared to mice inoculated with the other four strains. Our results suggest that, even though more human USUV disease cases have been reported in Europe recently, African USUV strains are also highly pathogenic.
欧洲和非洲的新兴arbovirus忽视了USUTU病毒的进化史和扩散的重建。
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