{"title":"Pair combinations of human monoclonal antibodies fully protected mice against bunyavirus SFTSV lethal challenge.","authors":"Bang Li, Xiang-Rong Qin, Jia-Chen Qu, Guan-du Wu, Wen-Kang Zhang, Ze-Zheng Jiang, Pan-Pan Liu, Ze-Min Li, Tian-Mei Yu, Chuan-Min Zhou, Yong-Jun Jiao, Xue-Jie Yu","doi":"10.1371/journal.ppat.1012889","DOIUrl":"10.1371/journal.ppat.1012889","url":null,"abstract":"<p><p>Severe fever with thrombocytopenia syndrome (SFTS) is a viral hemorrhagic fever caused by a tick-borne virus SFTSV with a mortality rate of up to 30%. Currently, there is no vaccine or effective therapy for SFTS. Neutralizing monoclonal antibody therapy, which provides immediate passive immunity and may limit disease progression, has emerged as a reliable approach for developing therapeutic drugs for SFTS. In this study, 4 human monoclonal antibodies (hmAbs) derived from convalescent SFTS patients' lymphocytes based on human single-chain variable fragment antibody libraries were tested for their neutralizing activities in cells and their treatment effect in animals individually and in pair combinations. The neutralization test showed that all 4 hmAbs exhibited strong neutralizing activity against SFTSV infection in vitro. The protection rate of hmAbs 4-6, 1F6, 1B2, and 4-5 against SFTSV lethal challenge in IFNAR1-/- A129 mice are 50%, 16.7%, 83.3%, and 66.7%, respectively. Notably, the pair combination of antibodies (1B2 and 4-5, 1B2 and 1F6) that recognized distinct epitopes protected 100% of mice against SFTSV lethal challenge. In conclusion, our findings indicate that the pair combinations of hmAbs 1B2 and 4-5 or hmAbs 1B2 and 1F6 may serve as promising therapeutic drugs for treating SFTSV infection.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012889"},"PeriodicalIF":5.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oxidative stress-driven enhanced iron production and scavenging through Ferroportin reorientation worsens anemia in antimony-resistant Leishmania donovani infection.","authors":"Souradeepa Ghosh, Krishna Vamshi Chigicherla, Shirin Dasgupta, Yasuyuki Goto, Budhaditya Mukherjee","doi":"10.1371/journal.ppat.1012858","DOIUrl":"10.1371/journal.ppat.1012858","url":null,"abstract":"<p><p>Despite the withdrawal of pentavalent-antimonials in treating Visceral leishmaniasis from India, recent clinical isolates of Leishmania donovani (LD) exhibit unresponsiveness towards pentavalent-antimony (LD-R). This antimony-unresponsiveness points towards a genetic adaptation that underpins LD-R's evolutionary persistence and dominance over sensitive counterparts (LD-S). This study highlights how LD evolutionarily tackled antimony exposure and gained increased potential of scavenging host-iron within its parasitophorous vacuoles (PV) to support its aggressive proliferation. Even though anti-leishmanial activity of pentavalent antimonials relies on triggering oxidative outburst, LD-R exhibits a surprising strategy of promoting reactive oxygen species (ROS) generation in infected macrophages. An inherent metabolic shift from glycolysis to Pentose Phosphate shunt allows LD-R to withstand elevated ROS by sustaining heightened levels of NADPH. Elevated ROS levels on the other hand trigger excess iron production, and LD-R capitalizes on this surplus iron by selectively reshuffling macrophage-surface iron exporter, Ferroportin, around its PV thereby gaining a survival edge as a heme-auxotroph. Higher iron utilization by LD-R leads to subsequent iron insufficiency, compensated by increased erythrophagocytosis through the breakdown of SIRPα-CD47 surveillance, orchestrated by a complex interplay of two proteases, Furin and ADAM10. Understanding these mechanisms is crucial for managing LD-R-infections and their associated complications like severe anemia, and may also provide valuable mechanistic insights into understanding drug unresponsiveness developed in other intracellular pathogens that rely on host iron.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012858"},"PeriodicalIF":5.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS PathogensPub Date : 2025-01-31eCollection Date: 2025-01-01DOI: 10.1371/journal.ppat.1012916
Gina L Griffith, Kawthar Machmach, Ningbo Jian, Dohoon Kim, Margaret C Costanzo, Matthew Creegan, Isabella Swafford, Gautam Kundu, Lauren Yum, Jessica S Bolton, Lauren Smith, Bonnie M Slike, Elke S Bergmann-Leitner, Rasmi Thomas, Nelson L Michael, Julie A Ake, Leigh Anne Eller, Merlin L Robb, Samantha M Townsley, Shelly J Krebs, Dominic Paquin-Proulx
{"title":"CD16 and CD57 expressing gamma delta T cells in acute HIV-1 infection are associated with the development of neutralization breadth.","authors":"Gina L Griffith, Kawthar Machmach, Ningbo Jian, Dohoon Kim, Margaret C Costanzo, Matthew Creegan, Isabella Swafford, Gautam Kundu, Lauren Yum, Jessica S Bolton, Lauren Smith, Bonnie M Slike, Elke S Bergmann-Leitner, Rasmi Thomas, Nelson L Michael, Julie A Ake, Leigh Anne Eller, Merlin L Robb, Samantha M Townsley, Shelly J Krebs, Dominic Paquin-Proulx","doi":"10.1371/journal.ppat.1012916","DOIUrl":"10.1371/journal.ppat.1012916","url":null,"abstract":"<p><p>New HIV vaccine approaches are focused on eliciting broadly neutralizing antibodies. We characterized early gamma-delta (γδ) T cell responses starting from pre-acquisition and during acute HIV infection (AHI) in participants previously characterized for neutralization breadth development. We found significant differences in γδ T cell surface marker expression in participants that developed neutralization breadth compared to those that did not. Activation of γδ T cells occurred within the first weeks of HIV acquisition and associated with viral load. Expression of CD16 on Vδ1 T cells and CD57 on Vδ2 T cells were found to be significantly higher in broad neutralizers during AHI, and associated with the development of neutralization breadth years later. In addition, the levels of CD16 on Vδ1 T cells was associated with early production of founder virus Env-specific IgM. Thus, γδ T cells may promote development of neutralization breadth, which has implications for HIV vaccine strategies.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012916"},"PeriodicalIF":5.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11805418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS PathogensPub Date : 2025-01-31eCollection Date: 2025-01-01DOI: 10.1371/journal.ppat.1012932
Lin Zhu, Yuqing Xie, Chenxi Liu, Jie Cheng, Zhongjian Shen, Xiaoming Liu, Limei Cai, Xinyuan Ning, Songdou Zhang, Zhen Li, Qiuying Huang, Xiaoxia Liu
{"title":"Baculoviruses manipulate host lipid metabolism via adipokinetic hormone signaling to induce climbing behavior.","authors":"Lin Zhu, Yuqing Xie, Chenxi Liu, Jie Cheng, Zhongjian Shen, Xiaoming Liu, Limei Cai, Xinyuan Ning, Songdou Zhang, Zhen Li, Qiuying Huang, Xiaoxia Liu","doi":"10.1371/journal.ppat.1012932","DOIUrl":"10.1371/journal.ppat.1012932","url":null,"abstract":"<p><p>Baculoviruses can induce climbing behavior in caterpillar hosts, which provides an excellent model for studying parasite manipulation of host behavior. Herein, we found that Helicoverpa armigera single nucleopolyhedrovirus (HearNPV) promoted lipid metabolism of infected H. armigera larvae, and changes in lipid metabolism can affect climbing behavior. Therefore, understanding the molecular mechanisms between lipid metabolism and climbing behavior is particularly important. In this study, we found adipokinetic hormone 1 (HaAKH1), adipokinetic hormone 2 (HaAKH2) and their receptor HaAKHR were essential for promoting lipid metabolism and climbing behavior in response to HearNPV infection. Both molecular docking result and Ca2+ imaging showed that both HaAKH1 and HaAKH2 could interact with HaAKHR. Knockdown of HaAKH1, HaAKH2 and HaAKHR resulted in not only the accumulation of triacylglycerol (TAG), but also the reduction of the replication of HearNPV and the crawling ability of infected H. armigera larvae, resulting in a decrease in the final death height of the infected larvae. We further validated this conclusion by injecting active peptides of HaAKH1 and HaAKH2 to infected larvae. In addition, we investigated the downstream of HaAKH signaling and found that hormone-sensitive lipase (HaHSL) changed with changes in HaAKH signaling and HaHSL played the same role as HaAKH signaling. These findings not only revealed the mechanism by which parasites manipulated host lipid metabolism, but more significantly, explored the relationship between lipid metabolism and behavioral changes of hosts manipulated by parasites, broadening our understanding of the phenomenon of parasites manipulating host behavioral changes.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012932"},"PeriodicalIF":5.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11819524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS PathogensPub Date : 2025-01-30eCollection Date: 2025-01-01DOI: 10.1371/journal.ppat.1012884
Haleema Sadia Malik, James B Bliska
{"title":"Guards and decoys: RIPoptosome and inflammasome pathway regulators of bacterial effector-triggered immunity.","authors":"Haleema Sadia Malik, James B Bliska","doi":"10.1371/journal.ppat.1012884","DOIUrl":"10.1371/journal.ppat.1012884","url":null,"abstract":"<p><p>Virulent microbes produce proteins that interact with host cell targets to promote pathogenesis. For example, virulent bacterial pathogens have proteins called effectors that are typically enzymes and are secreted into host cells. To detect and respond to the activities of effectors, diverse phyla of host organisms evolved effector-triggered immunity (ETI). In ETI, effectors are often sensed indirectly by detection of their virulence activities in host cells. ETI mechanisms can be complex and involve several classes of host proteins. Guards monitor the functional or physical integrity of another host protein, the guardee or decoy, and become activated to initiate an immune response when the guardee or decoy is modified or disrupted by an effector. A guardee typically has an intrinsic anti-pathogen function and is the intended target of an effector. A decoy structurally mimics a host protein that has intrinsic anti-pathogen activity and is unintentionally targeted by an effector. A decoy can be an individual protein, or a protein domain integrated into a guard. Here, we review the origins of ETI and focus on 5 mechanisms, in which the key steps of a pathway can include activation of a caspase by a RIPoptosome or inflammasome, formation of pores in the plasma membrane, release of cytokines and ending in cell death by pyroptosis. Survey of the 5 mechanisms, which have been shown to be host protective in mouse models of bacterial infection, reveal how distinct regulators of RIPoptosome or inflammasome pathways can act as guards or integrated decoys to trigger ETI. Common themes are highlighted and the limited mechanistic understanding of ETI bactericidal activity is discussed.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012884"},"PeriodicalIF":5.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Homeobox protein MSX-1 restricts hepatitis B virus by promoting ubiquitin-independent proteasomal degradation of HBx protein.","authors":"Qian Qiu, Zihan He, Jing Liu, Huijun Xu, Jinyu Wang, Nannan Liu, Ning Kang, Shaokun Pan, Weien Yu, Zixiang Gao, Shimei Zhang, Yang Yang, Qiang Deng, Youhua Xie, Jiming Zhang, Zhongliang Shen","doi":"10.1371/journal.ppat.1012897","DOIUrl":"10.1371/journal.ppat.1012897","url":null,"abstract":"<p><p>Hepatitis B virus (HBV) X protein (HBx) is a key factor for regulating viral transcription and replication. We recently characterized homeobox protein MSX-1 (MSX1) as a host restriction factor that inhibits HBV gene expression and genome replication by directly binding to HBV enhancer II/core promoter (EnII/Cp) and suppressing its promoter and enhancer activities. Notably, HBx expression was observed to be repressed more drastically by MSX1 compared to other viral antigens. In this work, we report that in addition to transcriptional repression, MSX1 also post-transcriptionally downregulates HBx protein stability. Mechanistically, MSX1 induces ubiquitin-independent proteasomal degradation of HBx, which is mediated through HBx C-terminal domain. Furthermore, this effect on HBx degradation correlates with MSX1-induced upregulation of DNAJA4 and CRYAB expression. Similar to MSX1, both DNAJA4 and CRYAB promote HBx degradation and repress HBV gene expression and genome replication. In chronic hepatitis B (CHB) patients, immune active phase (IA) is associated with higher intrahepatic expression of MSX1, DNAJA4 and CRYAB, and lower serum HBV markers compared to immune tolerant (IT) phase. Finally, HBV infection is significantly suppressed by MSX1 overexpression in both NTCP-overexpressing cell and humanized liver mouse models. These results demonstrate additional and novel mechanisms of MSX1-mediated repression of HBV, and establish MSX1 as a multi-functional HBV restriction factor with therapeutic potential.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012897"},"PeriodicalIF":5.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS PathogensPub Date : 2025-01-30eCollection Date: 2025-01-01DOI: 10.1371/journal.ppat.1012906
Santiago Boccardo, Constanza Rodriguez, Camila M S Gimenez, Cintia L Araujo Furlan, Carolina P Abrate, Laura Almada, Manuel A Saldivia Concepción, Peter Skewes-Cox, Srinivasa P S Rao, Jorge H Mukdsi, Carolina L Montes, Adriana Gruppi, Eva V Acosta Rodríguez
{"title":"Dynamics of tissue repair regulatory T cells and damage in acute Trypanosoma cruzi infection.","authors":"Santiago Boccardo, Constanza Rodriguez, Camila M S Gimenez, Cintia L Araujo Furlan, Carolina P Abrate, Laura Almada, Manuel A Saldivia Concepción, Peter Skewes-Cox, Srinivasa P S Rao, Jorge H Mukdsi, Carolina L Montes, Adriana Gruppi, Eva V Acosta Rodríguez","doi":"10.1371/journal.ppat.1012906","DOIUrl":"10.1371/journal.ppat.1012906","url":null,"abstract":"<p><p>Tissue-repair regulatory T cells (trTregs) comprise a specialized cell subset essential for tissue homeostasis and repair. While well-studied in sterile injury models, their role in infection-induced tissue damage and antimicrobial immunity is less understood. We investigated trTreg dynamics during acute Trypanosoma cruzi infection, marked by extensive tissue damage and strong CD8+ immunity. Unlike sterile injury models, trTregs significantly declined in secondary lymphoid organs and non-lymphoid target tissues during infection, correlating with systemic and local tissue damage, and downregulation of function-associated genes in skeletal muscle. This decline was linked to decreased systemic IL-33 levels, a key trTreg growth factor, and promoted by the Th1 cytokine IFN-γ. Early recombinant IL-33 treatment increased trTregs, type 2 innate lymphoid cells, and parasite-specific CD8+ cells at specific time points after infection, leading to reduced tissue damage, lower parasite burden, and improved disease outcome. Our findings not only provide novel insights into trTregs during infection but also highlight the potential of optimizing immune balance by modulating trTreg responses to promote tissue repair while maintaining effective pathogen control during infection-induced injury.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012906"},"PeriodicalIF":5.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS PathogensPub Date : 2025-01-30eCollection Date: 2025-01-01DOI: 10.1371/journal.ppat.1012892
A Manuel Liaci, Naresh Chandra, Sharvani Munender Vodnala, Michael Strebl, Pravin Kumar, Vanessa Pfenning, Paul Bachmann, Rémi Caraballo, Wengang Chai, Emil Johansson, Mikael Elofsson, Ten Feizi, Yan Liu, Thilo Stehle, Niklas Arnberg
{"title":"Extended receptor repertoire of an adenovirus associated with human obesity.","authors":"A Manuel Liaci, Naresh Chandra, Sharvani Munender Vodnala, Michael Strebl, Pravin Kumar, Vanessa Pfenning, Paul Bachmann, Rémi Caraballo, Wengang Chai, Emil Johansson, Mikael Elofsson, Ten Feizi, Yan Liu, Thilo Stehle, Niklas Arnberg","doi":"10.1371/journal.ppat.1012892","DOIUrl":"10.1371/journal.ppat.1012892","url":null,"abstract":"<p><p>Human adenovirus type 36 (HAdV-D36) has been putatively linked to obesity in animals and has been associated with obesity in humans in some but not all studies. Despite extensive epidemiological research there is limited information about its receptor profile. We investigated the receptor portfolio of HAdV-D36 using a combined structural biology and virology approach. The HAdV-D36 fiber knob domain (FK), which mediates the primary attachment of many HAdVs to host cells, has a significantly elongated DG loop that alters known binding interfaces for established adenovirus receptors such as the coxsackie- and adenovirus receptor (CAR) and CD46. Our data suggest that HAdV-D36 attaches to host cells using a versatile receptor pool comprising sialic acid-containing glycans and CAR. Sialic acids are recognized at the same binding site used by other HAdVs of species D such as HAdV-D37. Using glycan microarrays, we demonstrate that HAdV-D36 displays a binding preference for glycans containing a rare sialic acid variant, 4-O,5-N-diacetylneuraminic acid, over the more common 5-N-acetylneuraminic acid. To date, this sialic acid variant has not been detected in humans, although it can be synthesized by various animal species, including a range of domestic and livestock animals. Taken together, our results indicate that HAdV-D36 has evolved to recognize a specialized set of primary attachment receptors that are different from known HAdV types and coincides with a unique host range and pathogenicity profile.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012892"},"PeriodicalIF":5.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS PathogensPub Date : 2025-01-28eCollection Date: 2025-01-01DOI: 10.1371/journal.ppat.1012206
Tiana M Scott, Lydia M Arnold, Jordan A Powers, Delaney A McCann, Ana B Rowe, Devin E Christensen, Miguel J Pereira, Wen Zhou, Rachel M Torrez, Janet H Iwasa, Philip J Kranzusch, Wesley I Sundquist, Jarrod S Johnson
{"title":"Cell-free assays reveal that the HIV-1 capsid protects reverse transcripts from cGAS immune sensing.","authors":"Tiana M Scott, Lydia M Arnold, Jordan A Powers, Delaney A McCann, Ana B Rowe, Devin E Christensen, Miguel J Pereira, Wen Zhou, Rachel M Torrez, Janet H Iwasa, Philip J Kranzusch, Wesley I Sundquist, Jarrod S Johnson","doi":"10.1371/journal.ppat.1012206","DOIUrl":"10.1371/journal.ppat.1012206","url":null,"abstract":"<p><p>Retroviruses can be detected by the innate immune sensor cyclic GMP-AMP synthase (cGAS), which recognizes reverse-transcribed DNA and activates an antiviral response. However, the extent to which HIV-1 shields its genome from cGAS recognition remains unclear. To study this process in mechanistic detail, we reconstituted reverse transcription, genome release, and innate immune sensing of HIV-1 in a cell-free system. We found that wild-type HIV-1 capsids protect viral genomes from cGAS even after completing reverse transcription. Viral DNA could be \"deprotected\" by thermal stress, capsid mutations, or reduced concentrations of inositol hexakisphosphate (IP6) that destabilize the capsid. Strikingly, the capsid inhibitor lenacapavir also disrupted viral cores and dramatically potentiated cGAS activity, both in vitro and in cellular infections. Our results provide biochemical evidence that the HIV-1 capsid lattice conceals the genome from cGAS and that chemical or physical disruption of the viral core can expose HIV-1 DNA and activate innate immune signaling.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012206"},"PeriodicalIF":5.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11793794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS PathogensPub Date : 2025-01-27eCollection Date: 2025-01-01DOI: 10.1371/journal.ppat.1012831
Stefan Bresson, Emanuela Sani, Alicja Armatowska, Charles Dixon, David Tollervey
{"title":"The transcriptional and translational landscape of HCoV-OC43 infection.","authors":"Stefan Bresson, Emanuela Sani, Alicja Armatowska, Charles Dixon, David Tollervey","doi":"10.1371/journal.ppat.1012831","DOIUrl":"10.1371/journal.ppat.1012831","url":null,"abstract":"<p><p>The coronavirus HCoV-OC43 circulates continuously in the human population and is a frequent cause of the common cold. Here, we generated a high-resolution atlas of the transcriptional and translational landscape of OC43 during a time course following infection of human lung fibroblasts. Using ribosome profiling, we quantified the relative expression of the canonical open reading frames (ORFs) and identified previously unannotated ORFs. These included several potential short upstream ORFs and a putative ORF nested inside the M gene. In parallel, we analyzed the cellular response to infection. Endoplasmic reticulum (ER) stress response genes were transcriptionally and translationally induced beginning 12 and 18 hours post infection, respectively. By contrast, conventional antiviral genes mostly remained quiescent. At the same time points, we observed accumulation and increased translation of noncoding transcripts normally targeted by nonsense mediated decay (NMD), suggesting NMD is suppressed during the course of infection. This work provides resources for deeper understanding of OC43 gene expression and the cellular responses during infection.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 1","pages":"e1012831"},"PeriodicalIF":5.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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