Virulence mismatches in index hosts shape the outcomes of cross-species transmission.
Virulence mismatches in index hosts shape the outcomes of cross-species transmission.
复制标题
指标宿主的毒力不匹配影响跨物种传播的结果。
DOI：
10.1073/pnas.2006778117
复制
发表时间：
2020-11-17
影响因子：
11.1
通讯作者：
Biek R
中科院分区：
文献类型：
--
作者：
Mollentze N;Streicker DG;Murcia PR;Hampson K;Biek R
新出现的疾病流行通常是由于病原体在新的宿主物种中建立传播。然而，由于仍然知之甚少的原因，大多数跨物种传播未能在新感染的物种中建立。研究狂犬病病毒的实验性跨物种接种，我们发现宿主和病毒因素预测疾病进展的差异，预计会影响向前传播的可能性。当宿主和新宿主在生理学或遗传学上更不相似时，疾病进展加速，病毒排泄减少。这些见解可能有助于解释和预测狂犬病和其他人畜共患病毒的宿主转移，并强调实验接种数据的荟萃分析是了解指数感染动态的一种强大且可推广的方法。病原体进入新的宿主物种是否导致单一感染或向前传播，并可能爆发，取决于指示病例的感染进展。虽然指数感染是很少观察到的性质，实验性接种病原体到新的宿主物种提供了丰富的，很大程度上未开发的数据源的荟萃分析，以确定主机和病原体的感染结果的可变性的决定因素。我们分析了514次实验性狂犬病病毒跨物种接种的进展，狂犬病病毒是一种广泛的人畜共患病，在自然界中表现出死端感染和不同程度的持续传播。来自蝙蝠而不是食肉动物的接种，以及从温暖到凉爽的身体物种引起的感染潜伏期较短，与减少病毒排泄有关。远亲宿主之间的接种往往会导致较短的临床疾病期，这也有望阻止继续传播。所有影响均受感染剂量的调节。综上所述，这些结果表明，随着宿主物种变得越来越不相似，增加的毒力可能会作为一个限制因素，防止向前传播。这些结果可以解释观察到的狂犬病病毒宿主转移的限制，描述了以前未被认识到的宿主体温的作用，并提供了一个潜在的解释宿主转移是不太可能在遗传上遥远的物种之间。更一般地说，我们的研究强调了实验感染的荟萃分析作为一种易于处理的方法，以量化病毒，水库和新宿主之间的复杂相互作用，形成跨物种传播的结果。
Emerging disease epidemics often result from a pathogen establishing transmission in a novel host species. However, for reasons that remain poorly understood, most cross-species transmissions fail to establish in the newly infected species. Examining experimental cross-species inoculations of rabies virus, we show that host and viral factors predict differences in disease progression in ways that are expected to impact the likelihood of onward transmission. Disease progression was accelerated and virus excretion decreased when the reservoir and novel host were physiologically or genetically more dissimilar. These insights may help to explain and predict host shifts in rabies and other zoonotic viruses and highlight meta-analyses of experimental inoculation data as a powerful and generalizable approach for understanding the dynamics of index infections. Whether a pathogen entering a new host species results in a single infection or in onward transmission, and potentially an outbreak, depends upon the progression of infection in the index case. Although index infections are rarely observable in nature, experimental inoculations of pathogens into novel host species provide a rich and largely unexploited data source for meta-analyses to identify the host and pathogen determinants of variability in infection outcomes. We analyzed the progressions of 514 experimental cross-species inoculations of rabies virus, a widespread zoonosis which in nature exhibits both dead-end infections and varying levels of sustained transmission in novel hosts. Inoculations originating from bats rather than carnivores, and from warmer- to cooler-bodied species caused infections with shorter incubation periods that were associated with diminished virus excretion. Inoculations between distantly related hosts tended to result in shorter clinical disease periods, which are also expected to impede onward transmission. All effects were modulated by infection dose. Taken together, these results suggest that as host species become more dissimilar, increased virulence might act as a limiting factor preventing onward transmission. These results can explain observed constraints on rabies virus host shifts, describe a previously unrecognized role of host body temperature, and provide a potential explanation for host shifts being less likely between genetically distant species. More generally, our study highlights meta-analyses of experimental infections as a tractable approach to quantify the complex interactions between virus, reservoir, and novel host that shape the outcome of cross-species transmission.
登录
查看更多内容
影响因子：
5.2
作者：
Clarke, Andrew;Rothery, Peter
通讯作者：
Rothery, Peter
DOI：
10.1016/b978-0-12-396547-9.00005-5
发表时间：
2013-01-01
期刊：
RABIES: SCIENTIFIC BASIS OF THE DISEASE AND ITS MANAGEMENT, 3RD EDITION
影响因子：
--
作者：
Hanlon, Cathleen A.
通讯作者：
Hanlon, Cathleen A.
DOI：
10.1073/pnas.0708559104
发表时间：
2007-10-30
影响因子：
11.1
作者：
Fraser, Christophe;Hollingsworth, T. Deirdre;Hanage, William P.
通讯作者：
Hanage, William P.
DOI：
10.1073/pnas.0607968104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Gilbert, Gregory S.;Webb, Campbell O.
通讯作者：
Webb, Campbell O.
影响因子：
6.7
作者：
Longdon B;Hadfield JD;Day JP;Smith SC;McGonigle JE;Cogni R;Cao C;Jiggins FM
通讯作者：
Jiggins FM