Pub Date : 2023-12-29DOI: 10.1038/s41435-023-00250-7
Shelly J. Robertson, Sonja M. Best
{"title":"Interfer-on time: lessons from genetically diverse mouse models of SARS-CoV-2 infection","authors":"Shelly J. Robertson, Sonja M. Best","doi":"10.1038/s41435-023-00250-7","DOIUrl":"10.1038/s41435-023-00250-7","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-26DOI: 10.1038/s41435-023-00247-2
Henderson Zhu, Irina Chelysheva, Andrew J. Pollard, Daniel O’Connor
{"title":"Spotlight on systems vaccinology: a novel approach to elucidate correlates of protection","authors":"Henderson Zhu, Irina Chelysheva, Andrew J. Pollard, Daniel O’Connor","doi":"10.1038/s41435-023-00247-2","DOIUrl":"10.1038/s41435-023-00247-2","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-023-00247-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-25DOI: 10.1038/s41435-023-00243-6
José J. Fernández, Cristina Mancebo, Sonsoles Garcinuño, Gabriel March, Yolanda Alvarez, Sara Alonso, Luis Inglada, Jesús Blanco, Antonio Orduña, Olimpio Montero, Tito A. Sandoval, Juan R. Cubillos-Ruiz, Elena Bustamante-Munguira, Nieves Fernández, Mariano Sánchez Crespo
The utilization of host-cell machinery during SARS-CoV-2 infection can overwhelm the protein-folding capacity of the endoplasmic reticulum and activate the unfolded protein response (UPR). The IRE1α-XBP1 arm of the UPR could also be activated by viral RNA via Toll-like receptors. Based on these premises, a study to gain insight into the pathogenesis of COVID-19 disease was conducted using nasopharyngeal exudates and bronchioloalveolar aspirates. The presence of the mRNA of spliced XBP1 and a high expression of cytokine mRNAs were observed during active infection. TLR8 mRNA showed an overwhelming expression in comparison with TLR7 mRNA in bronchioloalveolar aspirates of COVID-19 patients, thus suggesting the presence of monocytes and monocyte-derived dendritic cells (MDDCs). In vitro experiments in MDDCs activated with ssRNA40, a synthetic mimic of SARS-CoV-2 RNA, showed induction of XBP1 splicing and the expression of proinflammatory cytokines. These responses were blunted by the IRE1α inhibitor MKC8866, the TLR8 antagonist CU-CPT9a, and knockdown of TLR8 receptor. In contrast, the IRE1α-XBP1 activator IXA4 enhanced these responses. Based on these findings, the TLR8/IRE1α system seems to play a significant role in the induction of the proinflammatory cytokines associated with severe COVID-19 disease and might be a druggable target to control cytokine storm.
{"title":"Innate IRE1α-XBP1 activation by viral single-stranded RNA and its influence on lung cytokine production during SARS-CoV-2 pneumonia","authors":"José J. Fernández, Cristina Mancebo, Sonsoles Garcinuño, Gabriel March, Yolanda Alvarez, Sara Alonso, Luis Inglada, Jesús Blanco, Antonio Orduña, Olimpio Montero, Tito A. Sandoval, Juan R. Cubillos-Ruiz, Elena Bustamante-Munguira, Nieves Fernández, Mariano Sánchez Crespo","doi":"10.1038/s41435-023-00243-6","DOIUrl":"10.1038/s41435-023-00243-6","url":null,"abstract":"The utilization of host-cell machinery during SARS-CoV-2 infection can overwhelm the protein-folding capacity of the endoplasmic reticulum and activate the unfolded protein response (UPR). The IRE1α-XBP1 arm of the UPR could also be activated by viral RNA via Toll-like receptors. Based on these premises, a study to gain insight into the pathogenesis of COVID-19 disease was conducted using nasopharyngeal exudates and bronchioloalveolar aspirates. The presence of the mRNA of spliced XBP1 and a high expression of cytokine mRNAs were observed during active infection. TLR8 mRNA showed an overwhelming expression in comparison with TLR7 mRNA in bronchioloalveolar aspirates of COVID-19 patients, thus suggesting the presence of monocytes and monocyte-derived dendritic cells (MDDCs). In vitro experiments in MDDCs activated with ssRNA40, a synthetic mimic of SARS-CoV-2 RNA, showed induction of XBP1 splicing and the expression of proinflammatory cytokines. These responses were blunted by the IRE1α inhibitor MKC8866, the TLR8 antagonist CU-CPT9a, and knockdown of TLR8 receptor. In contrast, the IRE1α-XBP1 activator IXA4 enhanced these responses. Based on these findings, the TLR8/IRE1α system seems to play a significant role in the induction of the proinflammatory cytokines associated with severe COVID-19 disease and might be a druggable target to control cytokine storm.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139036071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-25DOI: 10.1038/s41435-023-00246-3
Giorgia Bucciol, Isabelle Meyts
{"title":"Spotlight: “Human STAT2 deficiency: a severe defect of antiviral immunity”","authors":"Giorgia Bucciol, Isabelle Meyts","doi":"10.1038/s41435-023-00246-3","DOIUrl":"10.1038/s41435-023-00246-3","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139035890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-23DOI: 10.1038/s41435-023-00249-0
Maxime Rotival, Lluis Quintana-Murci
{"title":"Environmental variation and genetic diversity contribute to population differences in immune responses to SARS-CoV-2 and COVID-19 risk","authors":"Maxime Rotival, Lluis Quintana-Murci","doi":"10.1038/s41435-023-00249-0","DOIUrl":"10.1038/s41435-023-00249-0","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139028186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-23DOI: 10.1038/s41435-023-00242-7
Alba Garrido-Trigo, Marisol Veny, Azucena Salas
{"title":"Uncovering intestinal macrophages through the integration of single-cell and spatial transcriptomics","authors":"Alba Garrido-Trigo, Marisol Veny, Azucena Salas","doi":"10.1038/s41435-023-00242-7","DOIUrl":"10.1038/s41435-023-00242-7","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139028235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-22DOI: 10.1038/s41435-023-00244-5
Peter M. Bruno
{"title":"The genomics revolution comes to the immunopeptidome","authors":"Peter M. Bruno","doi":"10.1038/s41435-023-00244-5","DOIUrl":"10.1038/s41435-023-00244-5","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-023-00244-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138884811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-20DOI: 10.1038/s41435-023-00232-9
Kubra Uslu, Firat Ozcelik, Gokmen Zararsiz, Vahap Eldem, Ahu Cephe, Izem Olcay Sahin, Recep Civan Yuksel, Hilal Sipahioglu, Zuhal Ozer Simsek, Osman Baspinar, Hilal Akalin, Yasin Simsek, Kursat Gundogan, Nuri Tutar, Aynur Karayol Akin, Yusuf Ozkul, Orhan Yildiz, Munis Dundar
The COVID-19 pandemic remains a significant public health concern despite the new vaccines and therapeutics. The clinical course of acute SARS-CoV-2 infection is highly variable and influenced by several factors related to the virus and the host. Numerous genetic studies, including candidate gene, exome, and genome sequencing studies, genome-wide association studies, and other omics efforts, have proposed various Mendelian and non-Mendelian associations with COVID-19 course. In this study, we conducted whole-exome sequencing on 90 unvaccinated patients from Turkey with no known comorbidities associated with severe COVID-19. Of these patients, 30 had severe, 30 had moderate, and 30 had mild/asymptomatic disease. We identified rare variants in genes associated with SARS-CoV-2 susceptibility and pathogenesis, with an emphasis on genes related to the regulation of inflammation, and discussed these in the context of the clinical course of the patients. In addition, we compared the frequencies of common variants between each group. Even though no variant remained statistically significant after correction for multiple testing, we observed that certain previously associated genes and variants showed significant associations before correction. Our study contributes to the existing literature regarding the genetic susceptibility to SARS-CoV-2. Future studies would be beneficial characterizing the host genetic properties in different populations.
{"title":"Deciphering the host genetic factors conferring susceptibility to severe COVID-19 using exome sequencing","authors":"Kubra Uslu, Firat Ozcelik, Gokmen Zararsiz, Vahap Eldem, Ahu Cephe, Izem Olcay Sahin, Recep Civan Yuksel, Hilal Sipahioglu, Zuhal Ozer Simsek, Osman Baspinar, Hilal Akalin, Yasin Simsek, Kursat Gundogan, Nuri Tutar, Aynur Karayol Akin, Yusuf Ozkul, Orhan Yildiz, Munis Dundar","doi":"10.1038/s41435-023-00232-9","DOIUrl":"10.1038/s41435-023-00232-9","url":null,"abstract":"The COVID-19 pandemic remains a significant public health concern despite the new vaccines and therapeutics. The clinical course of acute SARS-CoV-2 infection is highly variable and influenced by several factors related to the virus and the host. Numerous genetic studies, including candidate gene, exome, and genome sequencing studies, genome-wide association studies, and other omics efforts, have proposed various Mendelian and non-Mendelian associations with COVID-19 course. In this study, we conducted whole-exome sequencing on 90 unvaccinated patients from Turkey with no known comorbidities associated with severe COVID-19. Of these patients, 30 had severe, 30 had moderate, and 30 had mild/asymptomatic disease. We identified rare variants in genes associated with SARS-CoV-2 susceptibility and pathogenesis, with an emphasis on genes related to the regulation of inflammation, and discussed these in the context of the clinical course of the patients. In addition, we compared the frequencies of common variants between each group. Even though no variant remained statistically significant after correction for multiple testing, we observed that certain previously associated genes and variants showed significant associations before correction. Our study contributes to the existing literature regarding the genetic susceptibility to SARS-CoV-2. Future studies would be beneficial characterizing the host genetic properties in different populations.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138821636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-19DOI: 10.1038/s41435-023-00219-6
Thomas R. Müller, Marcus Buggert
{"title":"Boosting SARS-CoV-2 immunity in immunocompromised individuals","authors":"Thomas R. Müller, Marcus Buggert","doi":"10.1038/s41435-023-00219-6","DOIUrl":"10.1038/s41435-023-00219-6","url":null,"abstract":"","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41435-023-00219-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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