Rapid evolution of the env gene leader sequence in cats naturally infected with feline immunodeficiency virus.

Rapid evolution of the env gene leader sequence in cats naturally infected with feline immunodeficiency virus.
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DOI:
10.1099/vir.0.000035
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发表时间:
2015-04
期刊:
The Journal of general virology
影响因子:
--
通讯作者:
Hosie MJ
Hosie MJ
中科院分区:
其他
文献类型:
--
作者:
Bęczkowski PM;Hughes J;Biek R;Litster A;Willett BJ;Hosie MJ

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分析猫免疫缺陷病毒(FIV)在宿主内水平的演变是很重要的,以解决病毒准种的多样性和组成是否影响疾病的进展。我们研究了宿主内的多样性和进化率的整个env和结构片段的env序列从连续的血液样本中获得43个自然感染的家猫,表现出不同的临床结果。我们在大多数猫中观察到FIV env显示出非常低的宿主内多样性水平。我们估计env以每年每个位点1.16×10−3个替换的速率进化,并证明重组序列比非重组序列进化得更快。FIV env基因V3-V5片段在健康猫中的进化速率明显高于在绝症猫中的进化速率。我们的研究提供了第一个证据,即env的前导序列,而不是V3-V5序列,具有最高的宿主内多样性和所有env片段的最高进化速率,与该区域处于遗传变异的强烈选择压力下一致。总体而言,FIV env在自然感染的猫中表现出相对较低的宿主内多样性,并且进化缓慢。在env的前导序列中观察到最大的进化速率。虽然遗传稳定性不一定是临床稳定性的先决条件,但与人类免疫缺陷病毒相比,FIV的遗传稳定性更高,这可能解释了为什么许多自然感染的猫不会迅速发展为艾滋病。
Analysing the evolution of feline immunodeficiency virus (FIV) at the intra-host level is important in order to address whether the diversity and composition of viral quasispecies affect disease progression. We examined the intra-host diversity and the evolutionary rates of the entire env and structural fragments of the env sequences obtained from sequential blood samples in 43 naturally infected domestic cats that displayed different clinical outcomes. We observed in the majority of cats that FIV env showed very low levels of intra-host diversity. We estimated that env evolved at a rate of 1.16×10−3 substitutions per site per year and demonstrated that recombinant sequences evolved faster than non-recombinant sequences. It was evident that the V3–V5 fragment of FIV env displayed higher evolutionary rates in healthy cats than in those with terminal illness. Our study provided the first evidence that the leader sequence of env, rather than the V3–V5 sequence, had the highest intra-host diversity and the highest evolutionary rate of all env fragments, consistent with this region being under a strong selective pressure for genetic variation. Overall, FIV env displayed relatively low intra-host diversity and evolved slowly in naturally infected cats. The maximum evolutionary rate was observed in the leader sequence of env. Although genetic stability is not necessarily a prerequisite for clinical stability, the higher genetic stability of FIV compared with human immunodeficiency virus might explain why many naturally infected cats do not progress rapidly to AIDS.
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