Identifying changes in selective constraints: host shifts in influenza.
Identifying changes in selective constraints: host shifts in influenza.
复制标题
DOI：
10.1371/journal.pcbi.1000564
复制
发表时间：
2009-11
影响因子：
4.3
通讯作者：
Goldstein RA
中科院分区：
文献类型：
--
作者：
Tamuri AU;Dos Reis M;Hay AJ;Goldstein RA
A型流感的天然宿主是水禽。通常，水禽病毒不适合在人群中感染和传播。有时，通过重组或通过整个宿主转移事件，来自水禽病毒的遗传物质被引入人群，引起世界范围的流行病。确定哪些突变允许禽源病毒在人群中成功传播，对于预测和控制流感大流行非常重要。在这里，我们描述了一种新的方法来确定这样的突变。我们使用逐位点非同质系统发育模型，该模型明确考虑了不同宿主和位置的氨基酸平衡频率的差异。我们确定了172个氨基酸位点的强有力的支持和518个网站的中度支持不同的选择限制在人类和鸟类病毒。我们发现的位点为研究禽流感病毒对人类宿主适应性的实验病毒学家提供了宝贵的资源。鉴定宿主转移所必需的序列变化将有助于我们预测各种菌株的大流行潜力。该方法具有广泛的适用性，调查的变化时，选择性的约束条件的变化是已知的。A型流感的天然宿主是水禽。有时候，禽流感病毒的基因组片段能够转移到人类宿主中，或者是全部转移到人类宿主中，或者是通过与先前经历过宿主转移事件的基因组片段结合转移到人类宿主中。这样的宿主转移事件可以在其免疫幼稚宿主中引起世界范围的大流行。为了使这些宿主转移建立稳定的谱系，病毒必须适应新的宿主。确定过去发生的变化可以提供有关这一过程如何发生的重要线索，以及如何针对新流感威胁进行监测。不幸的是，很难确定氨基酸是否由于适应新宿主而发生变化，或者变化是否通过随机漂移发生。在这里，我们描述了一种新的系统发育的方法来确定位置的选择压力施加在位置的性质已经改变了相应的主机移位事件。我们确定了一些基因组片段上的一组位置。我们所描述的方法是广泛的适用性时，选择性约束的变化的时间是事先已知的。
The natural reservoir of Influenza A is waterfowl. Normally, waterfowl viruses are not adapted to infect and spread in the human population. Sometimes, through reassortment or through whole host shift events, genetic material from waterfowl viruses is introduced into the human population causing worldwide pandemics. Identifying which mutations allow viruses from avian origin to spread successfully in the human population is of great importance in predicting and controlling influenza pandemics. Here we describe a novel approach to identify such mutations. We use a sitewise non-homogeneous phylogenetic model that explicitly takes into account differences in the equilibrium frequencies of amino acids in different hosts and locations. We identify 172 amino acid sites with strong support and 518 sites with moderate support of different selection constraints in human and avian viruses. The sites that we identify provide an invaluable resource to experimental virologists studying adaptation of avian flu viruses to the human host. Identification of the sequence changes necessary for host shifts would help us predict the pandemic potential of various strains. The method is of broad applicability to investigating changes in selective constraints when the timing of the changes is known. Influenza A's natural reservoir is waterfowl. Sometimes avian virus genomic segments are able to shift to a human host, either in toto or by combining with those that underwent a previous host shift event. Such host shift events can cause worldwide pandemics in their immunologically naive hosts. In order for these host shifts to establish a stable lineage, the virus has to adapt to the new host. Identifying the changes that have occurred in the past can provide important clues about how this process happens, and how surveillance for new influenza threats should be targeted. Unfortunately, it is difficult to determine whether an amino acid has changed due to adaptation to the new host or whether the change occurred through random drift. Here we describe a novel phylogenetic approach to identifying locations where the nature of the selective pressure exerted on the location has changed corresponding to the host shift event. We identify a set of locations on a number of the genomic segments. The approach we describe is of wide applicability when the timing of the change of selective constraints is known in advance.
登录
查看更多内容
影响因子：
10.7
作者：
Forsberg, R;Christiansen, FB
通讯作者：
Christiansen, FB
影响因子：
10.7
作者：
Gu, X
通讯作者：
Gu, X
影响因子：
3.9
作者：
dos Reis, Mario;Hay, Alan J.;Goldstein, Richard A.
通讯作者：
Goldstein, Richard A.
影响因子：
5.4
作者：
Boni, Maciei F.;Zhou, Yang;Holmes, Edward C.
通讯作者：
Holmes, Edward C.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y