Sequence diversity of dengue virus type 2 in brain and thymus of infected interferon receptor ko mice: implications for dengue virulence.
Sequence diversity of dengue virus type 2 in brain and thymus of infected interferon receptor ko mice: implications for dengue virulence.
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DOI：
10.1186/s12985-016-0658-4
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发表时间：
2016-11-30
期刊：
影响因子：
4.8
通讯作者：
Kurosu T
中科院分区：
文献类型：
--
作者：
Dhole P;Nakayama EE;Saito A;Limkittikul K;Phanthanawiboon S;Shioda T;Kurosu T
我们此前曾报道，登革热病毒的一种临床分离株能够在编码I型和II型干扰素受体基因敲除的小鼠(干扰素-α/β/γR KO小鼠)中引起急性期全身感染；相比之下，其他强毒株在这种小鼠中表现出缓慢的疾病进展，在感染后约20天(P.I.)产生致命感染。在本研究中，我们试图通过检测2型DENV临床分离株(DV2P04/08)在小鼠中的疾病进展来阐明疾病进展缓慢的动力学。观察DV2P04/08在感染小鼠不同时间点的组织分布。测定了器官组织的全基因组病毒序列。免疫后第6天，在非神经器官(包括腹膜渗出细胞、脾、肾、肝、肺和骨髓)中检测到高水平的病毒RNA(VRNA)，而在脑中检测不到。到第14天，除胸腺和脑外，大多数器官的vRNA水平随后下降。对原始P04/08和从小鼠脑和胸腺中回收的病毒的全基因组序列分析表明，既存在同义突变，也存在非同义突变。不同的小鼠在大脑中表现出不同的病毒种群。从一只小鼠脑中提取的vRNA序列与原始DV2P04/08疫苗几乎相同，表明DV2P04/08不需要适应脑内的生长。然而，在另一只小鼠的胸腺中观察到了准种(即在测序过程中被检测为明显的核苷酸混合的混合种群)，有趣的是，只有突变种群在感染的后期侵入大脑。这些结果表明，小鼠几乎成功地清除了非神经器官中的病毒，但未能清除脑中的病毒。虽然DV2P04/08感染的死亡原因可能是病毒入侵脑部所致，但其死亡过程在不同的小鼠身上是不同的。这项研究将为了解DENV在小鼠体内的疾病进展提供新的视角。本文的在线版本(doi：10.1186/s12985-0160658-4)包含补充材料，授权用户可以使用。
We previously reported that a clinical isolate of dengue virus (DENV) is capable of causing acute-phase systemic infection in mice harboring knockouts of the genes encoding type-I and -II interferon IFN receptors (IFN-α/β/γR KO mice); in contrast, other virulent DENV isolates exhibited slow disease progression in this mice, yielding lethal infection around 20 days post-infection (p.i.). In the present study, we sought to clarify the dynamics of slow disease progression by examining disease progression of a type-2 DENV clinical isolate (DV2P04/08) in mice. The tissue distributions of DV2P04/08 in several organs of infeted mice were examined at different time points. Whole genome viral sequences from organs were determined. At day 6 p.i., high levels of viral RNA (vRNA) were detected in non-neuronal organs (including peritoneal exudate cells (PECs), spleen, kidney, liver, lung, and bone marrow) but not in brain. By day 14 p.i, vRNA levels subsequently decreased in most organs, with the exception of thymus and brain. Sequence analysis of the whole genome of the original P04/08 and those of viruses recovered from mouse brain and thymus demonstrated the presence of both synonymous and non-synonymous mutations. Individual mice showed different virus populations in the brain. The vRNA sequence derived from brain of one mouse was nearly identical to the original DV2P04/08 inoculum, suggesting that there was no need for adaptation of DV2P04/08 for growth in the brain. However, quasispecies (that is, mixed populations, detected as apparent nucleotide mixtures during sequencing) were observed in the thymus of another mouse, and interestingly only mutant population invaded the brain at a late stage of infection. These results suggested that the mouse nearly succeeded in eliminating virus from non-neuronal organs but failed to do so from brain. Although the cause of death by DV2P04/08 infection is likely to be the result of virus invasion to brain, its processes to the death are different in individual mice. This study will provide a new insight into disease progression of DENV in mice. The online version of this article (doi:10.1186/s12985-016-0658-4) contains supplementary material, which is available to authorized users.
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DOI：
10.3390/v3091739
发表时间：
2011-09
期刊：
Viruses
影响因子：
--
作者：
Gebhard LG;Filomatori CV;Gamarnik AV
通讯作者：
Gamarnik AV
影响因子：
6.4
作者：
Schul, Wouter;Liu, Wei;Vasudevan, Subhash G.
通讯作者：
Vasudevan, Subhash G.
影响因子：
5.4
作者：
Lin, SR;Hsieh, SC;Wang, WK
通讯作者：
Wang, WK
影响因子：
5.4
作者：
Shresta, Sujan;Sharar, Kristin L.;Harris, Eva
通讯作者：
Harris, Eva
DOI：
10.1084/jem.189.1.179
发表时间：
1999-01-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Clynes R;Maizes JS;Guinamard R;Ono M;Takai T;Ravetch JV
通讯作者：
Ravetch JV