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MX2 forms nucleoporin-comprising cytoplasmic biomolecular condensates that lure viral capsids MX2 形成由核蛋白组成的细胞质生物分子凝聚体,引诱病毒外壳
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.002
George D. Moschonas, Louis Delhaye, Robin Cooreman, Franziska Hüsers, Anayat Bhat, Zoe Stylianidou, Elien De Bousser, Laure De Pryck, Hanna Grzesik, Delphine De Sutter, Eef Parthoens, Anne-Sophie De Smet, Aleksandra Maciejczuk, Saskia Lippens, Nico Callewaert, Linos Vandekerckhove, Zeger Debyser, Beate Sodeik, Sven Eyckerman, Xavier Saelens
Human myxovirus resistance 2 (MX2) can restrict HIV-1 and herpesviruses at a post-entry step through a process requiring an interaction between MX2 and the viral capsids. The involvement of other host cell factors, however, remains poorly understood. Here, we mapped the proximity interactome of MX2, revealing strong enrichment of phenylalanine-glycine (FG)-rich proteins related to the nuclear pore complex as well as proteins that are part of cytoplasmic ribonucleoprotein granules. MX2 interacted with these proteins to form multiprotein cytoplasmic biomolecular condensates that were essential for its anti-HIV-1 and anti-herpes simplex virus 1 (HSV-1) activity. MX2 condensate formation required the disordered N-terminal region and MX2 dimerization. Incoming HIV-1 and HSV-1 capsids associated with MX2 at these dynamic cytoplasmic biomolecular condensates, preventing nuclear entry of their viral genomes. Thus, MX2 forms cytoplasmic condensates that likely act as nuclear pore decoys, trapping capsids and inducing premature viral genome release to interfere with nuclear targeting of HIV-1 and HSV-1.
人类肌瘤病毒抵抗力 2(MX2)可通过 MX2 与病毒外壳之间的相互作用,在进入后阶段限制 HIV-1 和疱疹病毒。然而,人们对其他宿主细胞因子的参与仍然知之甚少。在这里,我们绘制了 MX2 的近距离相互作用组,发现与核孔复合体有关的富含苯丙氨酸-甘氨酸(FG)的蛋白质以及作为细胞质核糖核蛋白颗粒一部分的蛋白质大量富集。MX2 与这些蛋白相互作用,形成多蛋白细胞质生物分子凝聚体,这对其抗 HIV-1 和抗单纯疱疹病毒 1(HSV-1)的活性至关重要。MX2 凝聚物的形成需要无序的 N 端区域和 MX2 的二聚化。传入的 HIV-1 和 HSV-1 包囊与 MX2 在这些动态的细胞质生物分子凝聚体上结合,阻止了病毒基因组进入细胞核。因此,MX2 形成的细胞质凝聚体可能充当核孔诱饵,诱捕噬菌体并诱导病毒基因组过早释放,从而干扰 HIV-1 和 HSV-1 的核靶向作用。
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引用次数: 0
RNAi, a sword of plant seeds to combat viral infections RNAi,植物种子对抗病毒感染的利剑
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.08.019
Yan Wang, Yule Liu
Vertical transmission of plant viruses through seeds has been known for a century, yet the mechanism for seeds to combat viral infection remains unclear. In this issue of Cell Host & Microbe, Liu and Ding demonstrate the genetic requirement of RNA silencing (RNAi) pathway for plants to suppress seed transmission.
植物病毒通过种子垂直传播已有百年历史,但种子抗病毒感染的机制仍不清楚。在本期《细胞宿主与amp; 微生物》(Cell Host & Microbe)杂志上,刘和丁(音译)证明了植物抑制种子传播所需的 RNA 沉默(RNAi)遗传途径。
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引用次数: 0
Bacteria renew an OLD protein to cleave host tRNAs and block phage translation 细菌更新一种古老的蛋白质,以裂解宿主 tRNA 并阻止噬菌体翻译
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.006
Kyle D. Gibbs, Michele LeRoux
Anti-phage defenses must rapidly sense and respond to diverse viruses. A recent pair of papers in Nature reveal via structural and functional assays how the PARIS defense system, a recently discovered toxin-antitoxin system, senses phage-associated molecular patterns (PhAMPs), thereby activating an endonuclease toxin that cleaves tRNA to block phage replication.
抗噬菌体防御系统必须迅速感知并应对各种病毒。最近发表在《自然》(Nature)上的两篇论文通过结构和功能测试揭示了 PARIS 防御系统(一种最近发现的毒素-抗毒素系统)如何感知噬菌体相关分子模式(PhAMPs),从而激活内切酶毒素,裂解 tRNA 以阻止噬菌体复制。
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引用次数: 0
Mimicry games: NPC-like MX2 condensates trap viruses 模仿游戏类似 NPC 的 MX2 凝聚物捕获病毒
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.001
Junfeng Zhou, Wei Wei
Recent findings suggest that HIV-1 capsids mimic nuclear transport receptors to engage FG-nucleoporins for entry into host nuclei. In this issue of Cell Host & Microbe, Moschonas et al. report that MX2 forms cytoplasmic condensates comprising FG-nucleoporins resembling nuclear pore complexes to capture viral capsids and hinder their nuclear transport.
最近的研究结果表明,HIV-1 的噬菌体能模拟核转运受体,使 FG 核蛋白参与进入宿主细胞核。在本期《细胞宿主与amp; 微生物》(Cell Host & Microbe)杂志上,Moschonas 等人报告说,MX2 形成了由类似核孔复合体的 FG-核orins 组成的细胞质凝聚体,以捕获病毒衣壳并阻碍其核运输。
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引用次数: 0
To sense or not to sense, Paneth cell regulation of mucosal immunity 感知或不感知,Paneth 细胞对粘膜免疫的调控
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.005
Sebastian Weis, Irah L. King, Wolfgang Vivas
Paneth cells located within intestinal crypts support epithelial stem cells and immunity through growth factors and antimicrobial peptides. In this issue of Cell Host & Microbe, Wallaeys et al. report that TNF sensing by Paneth cells disrupts the unfolded protein response and decreases antimicrobial peptides, causing bacterial translocation and sepsis.
位于肠隐窝内的Paneth细胞通过生长因子和抗菌肽支持上皮干细胞和免疫。在本期《细胞、宿主与amp; 微生物》(Cell Host & Microbe)杂志上,Wallaeys 等人报告说,Paneth 细胞对 TNF 的感应会破坏未折叠蛋白反应并减少抗菌肽,从而导致细菌转移和败血症。
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引用次数: 0
Intestinal fungal-host interactions in promoting and maintaining health 肠道真菌与宿主在促进和保持健康方面的相互作用
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.010
Jennifer H. Hill, June L. Round
The resident microbiota are a key component of a healthy organism. The vast majority of microbiome studies have focused on bacterial members, which constitute a significant portion of resident microbial biomass. Recent studies have demonstrated how the fungal component of the microbiota, or the mycobiome, influences mammalian biology despite its low abundance compared to other microbes. Fungi are known for their pathogenic potential, yet fungi are also prominent colonizers in healthy states, highlighting their duality. We summarize the characteristics that define the gut mycobiome across life, the factors that can impact its composition, and studies that identify mechanisms of how fungi confer health benefits. The goal of this review is to synthesize our knowledge regarding the composition and function of a healthy mycobiome with a view to inspiring future therapeutic advances.
常驻微生物群是健康生物体的关键组成部分。绝大多数微生物组研究都侧重于细菌,因为细菌在常驻微生物生物量中占很大比例。最近的研究表明,微生物群中的真菌成分或真菌生物群如何影响哺乳动物的生物学,尽管与其他微生物相比,真菌的丰度较低。真菌以其潜在的致病性而闻名,但在健康状态下,真菌也是重要的定植者,这突出了真菌的双重性。我们总结了肠道真菌生物群在整个生命过程中的特征、影响其组成的因素以及确定真菌如何对健康有益的机制的研究。这篇综述的目的是综合我们对健康真菌生物群的组成和功能的认识,以启发未来的治疗进展。
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引用次数: 0
Immunity to fungi and vaccine considerations 真菌免疫和疫苗考虑因素
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.011
Alexander J. Whitehead, Therese Woodring, Bruce S. Klein
Fungal disease poses a growing threat to public health that our current antifungal therapies are not well equipped to meet. As the population of immunocompromised hosts expands, and ecological changes favor the emergence of fungal pathogens, the development of new antifungal agents, including vaccines, becomes a global priority. Here, we summarize recent advancements in the understanding of fungal pathogenesis, key features of the host antifungal immune response, and how these findings could be leveraged to design novel approaches to deadly fungal disease.
真菌病对公共健康的威胁日益严重,而我们目前的抗真菌疗法还不能很好地应对这一威胁。随着免疫力低下的宿主群体不断扩大,以及生态环境的变化有利于真菌病原体的出现,开发包括疫苗在内的新型抗真菌药物已成为全球的当务之急。在此,我们总结了对真菌致病机理认识的最新进展、宿主抗真菌免疫反应的关键特征,以及如何利用这些发现设计新型方法来治疗致命的真菌疾病。
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引用次数: 0
From dysbiosis to homeostasis: Oleic acid matters in the vagina 从菌群失调到平衡:油酸在阴道中的作用
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.007
Ri-hua Xie, Hao Liu, Cancan Qi, Yan He
The role of fatty acids in shaping vaginal microbiota remains unclear. In an issue of Cell, Zhu et al. use genomic and transcriptomic analyses to reveal that oleic acid (OA) selectively inhibits L. iners while promoting L. crispatus, suggesting new strategies for the treatment of bacterial vaginosis (BV).
脂肪酸在塑造阴道微生物群方面的作用仍不清楚。在一期《细胞》杂志上,Zhu 等人利用基因组和转录组分析揭示了油酸(OA)能选择性地抑制 L. iners,同时促进 L. crispatus,为治疗细菌性阴道病(BV)提出了新策略。
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引用次数: 0
Host-microbe interaction paradigms in acute and recurrent vulvovaginal candidiasis 急性和复发性外阴阴道念珠菌病的宿主-微生物相互作用范例
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.08.018
Jessie MacAlpine, Michail S. Lionakis
Candida spp. are members of the human mucosal microbiota that can cause opportunistic diseases ranging from superficial infections to life-threatening invasive candidiasis. In humans, the most common infection caused by Candida spp. is vulvovaginal candidiasis (VVC), which affects >70% of women at least once in their lifetime. Of those women, ∼5%–10% develop recurrent VVC (RVVC). In this review, we summarize our current understanding of the host and fungal factors that contribute to susceptibility to VVC and RVVC. We synthesize key findings that support the notion that disease symptoms are driven by neutrophil-associated dysfunction and immunopathology and describe how antifungal immune mechanisms in the vagina are distinct from other mucosal barrier sites. Finally, we highlight key, unanswered research areas within the field that can help us better understand the immunopathogenesis of this infection and facilitate the development of novel preventive, therapeutic, and/or vaccination strategies to combat these common, poorly understood diseases.
念珠菌属是人类粘膜微生物群中的一员,可引起从浅表感染到危及生命的侵袭性念珠菌病等各种机会性疾病。在人类中,念珠菌属引起的最常见感染是外阴阴道念珠菌病(VVC),70%的女性一生中至少会感染一次。在这些妇女中,有 5%-10%会反复感染外阴阴道念珠菌病(RVVC)。在这篇综述中,我们总结了目前对导致 VVC 和 RVVC 易感性的宿主和真菌因素的认识。我们综述了支持疾病症状由中性粒细胞相关功能障碍和免疫病理驱动这一观点的主要发现,并描述了阴道中的抗真菌免疫机制与其他粘膜屏障部位的不同之处。最后,我们强调了该领域中尚未解决的关键研究领域,这些领域可以帮助我们更好地了解这种感染的免疫发病机制,并促进新型预防、治疗和/或疫苗接种策略的开发,以防治这些常见的、鲜为人知的疾病。
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引用次数: 0
The RNA landscape of the human commensal Segatella copri reveals a small RNA essential for gut colonization 人类共生动物 Segatella copri 的 RNA 图谱揭示了肠道定植所必需的小 RNA
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-04 DOI: 10.1016/j.chom.2024.09.008
Youssef El Mouali, Caroline Tawk, Kun D. Huang, Lena Amend, Till Robin Lesker, Falk Ponath, Jörg Vogel, Till Strowig
The bacterium Segatella copri is a prevalent member of the human gut microbiota associated with health and disease states. However, the intrinsic factors that determine its ability to colonize the gut effectively remain largely unknown. By extensive transcriptome mapping of S. copri and examining human-derived samples, we discover a small RNA, which we name Segatella RNA colonization factor (SrcF), and show that SrcF is essential for S. copri gut colonization in gnotobiotic mice. SrcF regulates genes involved in nutrient acquisition, and complex carbohydrates, particularly fructans, control its expression. Furthermore, SrcF expression is strongly influenced by human microbiome composition and by the breakdown of fructans by cohabitating commensals, suggesting that the breakdown of complex carbohydrates mediates interspecies signaling among commensals beyond its established function in generating energy. Together, this study highlights the contribution of a small RNA as a critical regulator in gut colonization.
Segatella copri 细菌是人类肠道微生物群中的一种常见成员,与健康和疾病状态有关。然而,决定其有效定植肠道能力的内在因素在很大程度上仍然未知。通过对 S. copri 进行广泛的转录组图谱绘制和对人类来源样本的研究,我们发现了一种小 RNA,并将其命名为 Segatella RNA 定殖因子(SrcF)。SrcF 可调控涉及营养获取的基因,而复杂碳水化合物(尤其是果聚糖)可控制其表达。此外,SrcF 的表达还受到人类微生物群组成以及同居共生动物分解果聚糖的强烈影响,这表明复杂碳水化合物的分解在产生能量的既定功能之外,还介导了共生动物之间的种间信号传递。总之,这项研究强调了小 RNA 作为肠道定植关键调节因子的作用。
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Cell host & microbe
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