Pub Date : 2024-10-09DOI: 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.
{"title":"MX2 forms nucleoporin-comprising cytoplasmic biomolecular condensates that lure viral capsids","authors":"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","doi":"10.1016/j.chom.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.chom.2024.09.002","url":null,"abstract":"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.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":null,"pages":null},"PeriodicalIF":30.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 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.
{"title":"RNAi, a sword of plant seeds to combat viral infections","authors":"Yan Wang, Yule Liu","doi":"10.1016/j.chom.2024.08.019","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.019","url":null,"abstract":"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 <em>Cell Host & Microbe</em>, Liu and Ding demonstrate the genetic requirement of RNA silencing (RNAi) pathway for plants to suppress seed transmission.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":null,"pages":null},"PeriodicalIF":30.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 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.
{"title":"Mimicry games: NPC-like MX2 condensates trap viruses","authors":"Junfeng Zhou, Wei Wei","doi":"10.1016/j.chom.2024.09.001","DOIUrl":"https://doi.org/10.1016/j.chom.2024.09.001","url":null,"abstract":"Recent findings suggest that HIV-1 capsids mimic nuclear transport receptors to engage FG-nucleoporins for entry into host nuclei. In this issue of <em>Cell Host & Microbe</em>, 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.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":null,"pages":null},"PeriodicalIF":30.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 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.
{"title":"To sense or not to sense, Paneth cell regulation of mucosal immunity","authors":"Sebastian Weis, Irah L. King, Wolfgang Vivas","doi":"10.1016/j.chom.2024.09.005","DOIUrl":"https://doi.org/10.1016/j.chom.2024.09.005","url":null,"abstract":"Paneth cells located within intestinal crypts support epithelial stem cells and immunity through growth factors and antimicrobial peptides. In this issue of <em>Cell Host & Microbe</em>, Wallaeys et al. report that TNF sensing by Paneth cells disrupts the unfolded protein response and decreases antimicrobial peptides, causing bacterial translocation and sepsis.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":null,"pages":null},"PeriodicalIF":30.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 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。
{"title":"Bacteria renew an OLD protein to cleave host tRNAs and block phage translation","authors":"Kyle D. Gibbs, Michele LeRoux","doi":"10.1016/j.chom.2024.09.006","DOIUrl":"https://doi.org/10.1016/j.chom.2024.09.006","url":null,"abstract":"Anti-phage defenses must rapidly sense and respond to diverse viruses. A recent pair of papers in <em>Nature</em> 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.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":null,"pages":null},"PeriodicalIF":30.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 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.
{"title":"Intestinal fungal-host interactions in promoting and maintaining health","authors":"Jennifer H. Hill, June L. Round","doi":"10.1016/j.chom.2024.09.010","DOIUrl":"https://doi.org/10.1016/j.chom.2024.09.010","url":null,"abstract":"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.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":null,"pages":null},"PeriodicalIF":30.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 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.
{"title":"Immunity to fungi and vaccine considerations","authors":"Alexander J. Whitehead, Therese Woodring, Bruce S. Klein","doi":"10.1016/j.chom.2024.09.011","DOIUrl":"https://doi.org/10.1016/j.chom.2024.09.011","url":null,"abstract":"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.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":null,"pages":null},"PeriodicalIF":30.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 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。
{"title":"From dysbiosis to homeostasis: Oleic acid matters in the vagina","authors":"Ri-hua Xie, Hao Liu, Cancan Qi, Yan He","doi":"10.1016/j.chom.2024.09.007","DOIUrl":"https://doi.org/10.1016/j.chom.2024.09.007","url":null,"abstract":"The role of fatty acids in shaping vaginal microbiota remains unclear. In an issue of <em>Cell</em>, Zhu et al. use genomic and transcriptomic analyses to reveal that oleic acid (OA) selectively inhibits <em>L. iners</em> while promoting <em>L. crispatus</em>, suggesting new strategies for the treatment of bacterial vaginosis (BV).","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":null,"pages":null},"PeriodicalIF":30.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 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.
{"title":"Host-microbe interaction paradigms in acute and recurrent vulvovaginal candidiasis","authors":"Jessie MacAlpine, Michail S. Lionakis","doi":"10.1016/j.chom.2024.08.018","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.018","url":null,"abstract":"<em>Candida</em> 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 <em>Candida</em> 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.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":null,"pages":null},"PeriodicalIF":30.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-04DOI: 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.
{"title":"The RNA landscape of the human commensal Segatella copri reveals a small RNA essential for gut colonization","authors":"Youssef El Mouali, Caroline Tawk, Kun D. Huang, Lena Amend, Till Robin Lesker, Falk Ponath, Jörg Vogel, Till Strowig","doi":"10.1016/j.chom.2024.09.008","DOIUrl":"https://doi.org/10.1016/j.chom.2024.09.008","url":null,"abstract":"The bacterium <em>Segatella copri</em> 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 <em>S. copri</em> and examining human-derived samples, we discover a small RNA, which we name <em>Segatella</em> RNA colonization factor (SrcF), and show that SrcF is essential for <em>S. copri</em> 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.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":null,"pages":null},"PeriodicalIF":30.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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