Cell host & microbePub Date : 2023-11-08Epub Date: 2023-10-27DOI: 10.1016/j.chom.2023.10.002
Daniel Paiva Agustinho, Holly Leanne Brown, Guohua Chen, Elizabeth Anne Gaylord, Jennifer Geddes-McAlister, Michael Richard Brent, Tamara Lea Doering
{"title":"Unbiased discovery of natural sequence variants that influence fungal virulence.","authors":"Daniel Paiva Agustinho, Holly Leanne Brown, Guohua Chen, Elizabeth Anne Gaylord, Jennifer Geddes-McAlister, Michael Richard Brent, Tamara Lea Doering","doi":"10.1016/j.chom.2023.10.002","DOIUrl":"10.1016/j.chom.2023.10.002","url":null,"abstract":"<p><p>Isolates of Cryptococcus neoformans, a fungal pathogen that kills over 112,000 people each year, differ from a 19-Mb reference genome at a few thousand up to almost a million DNA sequence positions. We used bulked segregant analysis and association analysis, genetic methods that require no prior knowledge of sequence function, to address the key question of which naturally occurring sequence variants influence fungal virulence. We identified a region containing such variants, prioritized them, and engineered strains to test our findings in a mouse model of infection. At one locus, we identified a 4-nt variant in the PDE2 gene that occurs in common laboratory strains and severely truncates the encoded phosphodiesterase. The resulting loss of phosphodiesterase activity significantly impacts virulence. Our studies demonstrate a powerful and unbiased strategy for identifying key genomic regions in the absence of prior information and provide significant sequence and strain resources to the community.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1910-1920.e5"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66784768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Harnessing the post-vaccination era: Do emerging HPV types represent a new threat?","authors":"Sergio Ponce-de-Leon, Marcela Lizano","doi":"10.1016/j.chom.2023.10.013","DOIUrl":"10.1016/j.chom.2023.10.013","url":null,"abstract":"<p><p>While the HPV vaccine is highly effective, it is unknown whether other, untargeted viral types could occupy empty niches to become an emerging threat. In this issue of Cell Host & Microbe, Pimenoff and colleagues present a community-level epidemiological analysis of HPV types up to 8 years after different vaccination policies.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":"31 11","pages":"1774-1775"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72016395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Athanasios Ziogas, Mariolina Bruno, Roy van der Meel, Willem J M Mulder, Mihai G Netea
{"title":"Trained immunity: Target for prophylaxis and therapy.","authors":"Athanasios Ziogas, Mariolina Bruno, Roy van der Meel, Willem J M Mulder, Mihai G Netea","doi":"10.1016/j.chom.2023.10.015","DOIUrl":"10.1016/j.chom.2023.10.015","url":null,"abstract":"<p><p>Trained immunity is a de facto memory for innate immune responses, leading to long-term functional reprogramming of innate immune cells. In physiological conditions, trained immunity leads to adaptive states that enhance resistance against pathogens and contributes to immunosurveillance. Dysregulated trained immunity can however lead either to defective innate immune responses in severe infections or cancer or to inflammatory and autoimmune diseases if trained immunity is inappropriately activated. Here, we review the immunological and molecular mechanisms that mediate trained immunity induction and propose that trained immunity represents an important target for prophylactic and therapeutic approaches in human diseases. On the one hand, we argue that novel approaches that induce trained immunity may enhance vaccine efficacy. On the other hand, induction of trained immunity in cancer, and inhibition of exaggerated induction of trained immunity in inflammatory disorders, are viable targets amenable for new therapeutic approaches.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":"31 11","pages":"1776-1791"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72016370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Putting the pieces together: Chimeric virus strategy decode Dengue virus 3 antibody responses.","authors":"Naoko Uno, Ted M Ross","doi":"10.1016/j.chom.2023.10.014","DOIUrl":"10.1016/j.chom.2023.10.014","url":null,"abstract":"<p><p>In this issue of Cell Host & Microbe, Munt et al. shed light on variability in human immune responses after natural infection compared to vaccination by using a recombinant virus platform that expresses chimeric Dengue virus type 1 and type 3 envelope proteins to identify and characterize type-specific neutralizing antibodies.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":"31 11","pages":"1772-1773"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72016399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ming-Yu Wang, Jun-Bin Chen, Rui Wu, Hai-Long Guo, Yan Chen, Zhen-Ju Li, Lu-Yang Wei, Chuang Liu, Sheng-Feng He, Mei-Da Du, Ya-Long Guo, You-Liang Peng, Jonathan D G Jones, Detlef Weigel, Jian-Hua Huang, Wang-Sheng Zhu
{"title":"The plant immune receptor SNC1 monitors helper NLRs targeted by a bacterial effector.","authors":"Ming-Yu Wang, Jun-Bin Chen, Rui Wu, Hai-Long Guo, Yan Chen, Zhen-Ju Li, Lu-Yang Wei, Chuang Liu, Sheng-Feng He, Mei-Da Du, Ya-Long Guo, You-Liang Peng, Jonathan D G Jones, Detlef Weigel, Jian-Hua Huang, Wang-Sheng Zhu","doi":"10.1016/j.chom.2023.10.006","DOIUrl":"10.1016/j.chom.2023.10.006","url":null,"abstract":"<p><p>Plants deploy intracellular receptors to counteract pathogen effectors that suppress cell-surface-receptor-mediated immunity. To what extent pathogens manipulate intracellular receptor-mediated immunity, and how plants tackle such manipulation, remains unknown. Arabidopsis thaliana encodes three similar ADR1 class helper nucleotide-binding domain leucine-rich repeat receptors (ADR1, ADR1-L1, and ADR1-L2), which are crucial in plant immunity initiated by intracellular receptors. Here, we report that Pseudomonas syringae effector AvrPtoB suppresses ADR1-L1- and ADR1-L2-mediated cell death. ADR1, however, evades such suppression by diversifying into two ubiquitination sites targeted by AvrPtoB. The intracellular sensor SNC1 interacts with and guards the CC<sub>R</sub> domains of ADR1-L1/L2. Removal of ADR1-L1/L2 or delivery of AvrPtoB activates SNC1, which then signals through ADR1 to trigger immunity. Our work elucidates the long-sought-after function of SNC1 in defense, and also how plants can use dual strategies, sequence diversification, and a multi-layered guard-guardee system, to counteract pathogen's attack on core immunity functions.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":"31 11","pages":"1792-1803.e7"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72016369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A gB nanoparticle vaccine elicits a protective neutralizing antibody response against EBV.","authors":"Cong Sun, Yin-Feng Kang, Xin-Yan Fang, Yi-Na Liu, Guo-Long Bu, Ao-Jie Wang, Yan Li, Qian-Ying Zhu, Hua Zhang, Chu Xie, Xiang-Wei Kong, Yong-Jian Peng, Wen-Jie Lin, Ling Zhou, Xin-Chun Chen, Zheng-Zhou Lu, Hui-Qin Xu, Dong-Chun Hong, Xiao Zhang, Ling Zhong, Guo-Kai Feng, Yi-Xin Zeng, Miao Xu, Qian Zhong, Zheng Liu, Mu-Sheng Zeng","doi":"10.1016/j.chom.2023.09.011","DOIUrl":"10.1016/j.chom.2023.09.011","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) is a global public health concern, as it is known to cause multiple diseases while also being etiologically associated with a wide range of epithelial and lymphoid malignancies. Currently, there is no available prophylactic vaccine against EBV. gB is the EBV fusion protein that mediates viral membrane fusion and participates in host recognition, making it critical for EBV infection in both B cells and epithelial cells. Here, we present a gB nanoparticle, gB-I53-50 NP, that displays multiple copies of gB. Compared with the gB trimer, gB-I53-50 NP shows improved structural integrity and stability, as well as enhanced immunogenicity in mice and non-human primate (NHP) preclinical models. Immunization and passive transfer demonstrate a robust and durable protective antibody response that protects humanized mice against lethal EBV challenge. This vaccine candidate demonstrates significant potential in preventing EBV infection, providing a possible platform for developing prophylactic vaccines for EBV.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1882-1897.e10"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41242160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell host & microbePub Date : 2023-11-08Epub Date: 2023-10-16DOI: 10.1016/j.chom.2023.09.010
Shanshan Liu, Liru Guan, Cheng Peng, Yuanna Cheng, Hongyu Cheng, Fei Wang, Mingtong Ma, Ruijuan Zheng, Zhe Ji, Pengfei Cui, Yefei Ren, Liru Li, Chenyue Shi, Jie Wang, Xiaochen Huang, Xia Cai, Di Qu, Haiping Zhang, Zhiyong Mao, Haipeng Liu, Peng Wang, Wei Sha, Hua Yang, Lin Wang, Baoxue Ge
{"title":"Mycobacterium tuberculosis suppresses host DNA repair to boost its intracellular survival.","authors":"Shanshan Liu, Liru Guan, Cheng Peng, Yuanna Cheng, Hongyu Cheng, Fei Wang, Mingtong Ma, Ruijuan Zheng, Zhe Ji, Pengfei Cui, Yefei Ren, Liru Li, Chenyue Shi, Jie Wang, Xiaochen Huang, Xia Cai, Di Qu, Haiping Zhang, Zhiyong Mao, Haipeng Liu, Peng Wang, Wei Sha, Hua Yang, Lin Wang, Baoxue Ge","doi":"10.1016/j.chom.2023.09.010","DOIUrl":"10.1016/j.chom.2023.09.010","url":null,"abstract":"<p><p>Mycobacterium tuberculosis (Mtb) triggers distinct changes in macrophages, resulting in the formation of lipid droplets that serve as a nutrient source. We discover that Mtb promotes lipid droplets by inhibiting DNA repair responses, resulting in the activation of the type-I IFN pathway and scavenger receptor-A1 (SR-A1)-mediated lipid droplet formation. Bacterial urease C (UreC, Rv1850) inhibits host DNA repair by interacting with RuvB-like protein 2 (RUVBL2) and impeding the formation of the RUVBL1-RUVBL2-RAD51 DNA repair complex. The suppression of this repair pathway increases the abundance of micronuclei that trigger the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway and subsequent interferon-β (IFN-β) production. UreC-mediated activation of the IFN-β pathway upregulates the expression of SR-A1 to form lipid droplets that facilitate Mtb replication. UreC inhibition via a urease inhibitor impaired Mtb growth within macrophages and in vivo. Thus, our findings identify mechanisms by which Mtb triggers a cascade of cellular events that establish a nutrient-rich replicative niche.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1820-1836.e10"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41242161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell host & microbePub Date : 2023-11-08Epub Date: 2023-10-25DOI: 10.1016/j.chom.2023.09.012
Kathryn E Kistler, Trevor Bedford
{"title":"An atlas of continuous adaptive evolution in endemic human viruses.","authors":"Kathryn E Kistler, Trevor Bedford","doi":"10.1016/j.chom.2023.09.012","DOIUrl":"10.1016/j.chom.2023.09.012","url":null,"abstract":"<p><p>Through antigenic evolution, viruses such as seasonal influenza evade recognition by neutralizing antibodies. This means that a person with antibodies well tuned to an initial infection will not be protected against the same virus years later and that vaccine-mediated protection will decay. To expand our understanding of which endemic human viruses evolve in this fashion, we assess adaptive evolution across the genome of 28 endemic viruses spanning a wide range of viral families and transmission modes. Surface proteins consistently show the highest rates of adaptation, and ten viruses in this panel are estimated to undergo antigenic evolution to selectively fix mutations that enable the escape of prior immunity. Thus, antibody evasion is not an uncommon evolutionary strategy among human viruses, and monitoring this evolution will inform future vaccine efforts. Additionally, by comparing overall amino acid substitution rates, we show that SARS-CoV-2 is accumulating protein-coding changes at substantially faster rates than endemic viruses.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1898-1909.e3"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular basis for inhibition of type III-B CRISPR-Cas by an archaeal viral anti-CRISPR protein.","authors":"Jinzhong Lin, Lauge Alfastsen, Yuvaraj Bhoobalan-Chitty, Xu Peng","doi":"10.1016/j.chom.2023.10.003","DOIUrl":"10.1016/j.chom.2023.10.003","url":null,"abstract":"<p><p>Despite a wide presence of type III clustered regularly interspaced short palindromic repeats, CRISPR-associated (CRISPR-Cas) in archaea and bacteria, very few anti-CRISPR (Acr) proteins inhibiting type III immunity have been identified, and even less is known about their inhibition mechanism. Here, we present the discovery of a type III CRISPR-Cas inhibitor, AcrIIIB2, encoded by Sulfolobus virus S. islandicus rod-shaped virus 3 (SIRV3). AcrIIIB2 inhibits type III-B CRISPR-Cas immune response to protospacers encoded in middle/late-expressed viral genes. Investigation of the interactions between S. islandicus type III-B CRISPR-Cas Cmr-α-related proteins and AcrIIIB2 reveals that the Acr does not bind to Csx1 but rather interacts with the Cmr-α effector complex. Furthermore, in vitro assays demonstrate that AcrIIIB2 can block the dissociation of cleaved target RNA from the Cmr-α complex, thereby inhibiting the Cmr-α turnover, thus preventing host cellular dormancy and further viral genome degradation by the type III-B CRISPR-Cas immunity.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1837-1849.e5"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71430183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bug in the code: TB blocks DNA repair.","authors":"Bala T S A Madduri, Samantha L Bell","doi":"10.1016/j.chom.2023.10.012","DOIUrl":"10.1016/j.chom.2023.10.012","url":null,"abstract":"<p><p>Protecting the cell's genome is crucial for survival, but infection causes damage that compromises genetic integrity. In this issue of Cell Host & Microbe, Lui et al. dissect how Mycobacterium tuberculosis exploits DNA damage using a secreted protein that inhibits DNA repair to create an environment conducive to bacterial replication.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":"31 11","pages":"1769-1771"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72016394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}