Suppr超能文献

PIWI 沉默机制涉及逆转录转座子 nimbus,协调了蜗牛载体光滑双脐螺对曼氏血吸虫感染的抗性。

PIWI silencing mechanism involving the retrotransposon nimbus orchestrates resistance to infection with Schistosoma mansoni in the snail vector, Biomphalaria glabrata.

机构信息

Howard University, Washington, District of Columbia, United States of America.

Division of Science & Mathematics, University of the District of Columbia, Washington, District of Columbia, United States of America.

出版信息

PLoS Negl Trop Dis. 2021 Sep 8;15(9):e0009094. doi: 10.1371/journal.pntd.0009094. eCollection 2021 Sep.

Abstract

BACKGROUND

Schistosomiasis remains widespread in many regions despite efforts at its elimination. By examining changes in the transcriptome at the host-pathogen interface in the snail Biomphalaria glabrata and the blood fluke Schistosoma mansoni, we previously demonstrated that an early stress response in juvenile snails, manifested by induction of heat shock protein 70 (Hsp 70) and Hsp 90 and of the reverse transcriptase (RT) domain of the B. glabrata non-LTR- retrotransposon, nimbus, were critical for B. glabrata susceptibility to S. mansoni. Subsequently, juvenile B. glabrata BS-90 snails, resistant to S. mansoni at 25°C become susceptible by the F2 generation when maintained at 32°C, indicating an epigenetic response.

METHODOLOGY/PRINCIPAL FINDINGS: To better understand this plasticity in susceptibility of the BS-90 snail, mRNA sequences were examined from S. mansoni exposed juvenile BS-90 snails cultured either at 25°C (non-permissive temperature) or 32°C (permissive). Comparative analysis of transcriptomes from snails cultured at the non-permissive and permissive temperatures revealed that whereas stress related transcripts dominated the transcriptome of susceptible BS-90 juvenile snails at 32°C, transcripts encoding proteins with a role in epigenetics, such as PIWI (BgPiwi), chromobox protein homolog 1 (BgCBx1), histone acetyltransferase (BgHAT), histone deacetylase (BgHDAC) and metallotransferase (BgMT) were highly expressed in those cultured at 25°C. To identify robust candidate transcripts that will underscore the anti-schistosome phenotype in B. glabrata, further validation of the differential expression of the above transcripts was performed by using the resistant BS-90 (25°C) and the BBO2 susceptible snail stock whose genome has now been sequenced and represents an invaluable resource for molecular studies in B. glabrata. A role for BgPiwi in B. glabrata susceptibility to S. mansoni, was further examined by using siRNA corresponding to the BgPiwi encoding transcript to suppress expression of BgPiwi, rendering the resistant BS-90 juvenile snail susceptible to infection at 25°C. Given transposon silencing activity of PIWI as a facet of its role as guardian of the integrity of the genome, we examined the expression of the nimbus RT encoding transcript at 120 min after infection of resistant BS90 piwi-siRNA treated snails. We observed that nimbus RT was upregulated, indicating that modulation of the transcription of the nimbus RT was associated with susceptibility to S. mansoni in BgPiwi-siRNA treated BS-90 snails. Furthermore, treatment of susceptible BBO2 snails with the RT inhibitor lamivudine, before exposure to S. mansoni, blocked S. mansoni infection concurrent with downregulation of the nimbus RT transcript and upregulation of the BgPiwi encoding transcript in the lamivudine-treated, schistosome-exposed susceptible snails.

CONCLUSIONS AND SIGNIFICANCE

These findings support a role for the interplay of BgPiwi and nimbus in the epigenetic modulation of plasticity of resistance/susceptibility in the snail-schistosome relationship.

摘要

背景

尽管已经在努力消除血吸虫病,但在许多地区它仍然广泛存在。通过研究在蜗牛 Bgabrata 和血吸虫 S. mansoni 的宿主-病原体界面转录组的变化,我们之前证明了幼年蜗牛的早期应激反应,表现为热休克蛋白 70(Hsp 70)和 Hsp 90 的诱导,以及 Bgabrata 非 LTR-反转录转座子 nimbus 的逆转录酶(RT)结构域,对于 Bgabrata 对 S. mansoni 的易感性至关重要。随后,在 25°C 下对 S. mansoni 具有抗性的幼年 Bgabrata BS-90 蜗牛在维持在 32°C 时通过 F2 代变得易感,这表明存在表观遗传反应。

方法/主要发现:为了更好地了解 BS-90 蜗牛易感性的这种可塑性,我们从在 25°C(非允许温度)或 32°C(允许温度)培养的暴露于 S. mansoni 的幼年 BS-90 蜗牛中检查了 mRNA 序列。在非允许和允许温度下培养的蜗牛的转录组的比较分析表明,尽管在 32°C 时易感 BS-90 幼年蜗牛的转录组以应激相关转录物为主,但在 25°C 下培养的转录物编码参与表观遗传学的蛋白质,如 PIWI(BgPiwi)、染色质盒蛋白同源物 1(BgCBx1)、组蛋白乙酰转移酶(BgHAT)、组蛋白去乙酰化酶(BgHDAC)和金属转移酶(BgMT)。为了鉴定将突出 Bgabrata 抗血吸虫表型的稳健候选转录本,我们进一步通过使用抗性 BS-90(25°C)和 BBO2 易感蜗牛品系验证了上述转录本的差异表达,其基因组现已测序,代表了 Bgabrata 分子研究的宝贵资源。BgPiwi 在 Bgabrata 对 S. mansoni 的易感性中的作用进一步通过使用针对 BgPiwi 编码转录本的 siRNA 进行了研究,该 siRNA 抑制 BgPiwi 的表达,使抗性 BS-90 幼年蜗牛在 25°C 下易感。鉴于 PIWI 的转座子沉默活性是其作为基因组完整性守护者的作用的一个方面,我们在感染抵抗性 BS90 piwi-siRNA 处理的蜗牛 120 分钟后检查了 nimbus RT 编码转录本的表达。我们观察到 nimbus RT 上调,表明 nimbus RT 的转录调控与 BgPiwi-siRNA 处理的 BS-90 蜗牛对 S. mansoni 的易感性相关。此外,在暴露于 S. mansoni 之前,用 RT 抑制剂拉米夫定处理易感 BBO2 蜗牛,可阻止 S. mansoni 感染,同时下调拉米夫定处理、感染血吸虫的易感蜗牛中的 nimbus RT 转录本,并上调 BgPiwi 编码转录本。

结论和意义

这些发现支持 BgPiwi 和 nimbus 的相互作用在蜗牛-血吸虫关系中对抵抗/易感性的可塑性的表观遗传调节中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0af3/8462715/8e01bb159500/pntd.0009094.g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验