The Journal of Infectious Diseases最新文献_第5页

Human Papillomavirus Persistence, Recurrence, and Incidence in Early Childhood. 人乳头瘤病毒在幼儿期的持续性、复发和发病率。

The Journal of Infectious Diseases Pub Date : 2025-05-14 DOI: 10.1093/infdis/jiaf213

Eméra Alice Bénard,Ana Maria Carceller,Marie-Hélène Mayrand,Jacques Lacroix,Joseph Niyibizi,Louise Laporte,François Audibert,François Coutlée,Helen Trottier,

{"title":"Human Papillomavirus Persistence, Recurrence, and Incidence in Early Childhood.","authors":"Eméra Alice Bénard,Ana Maria Carceller,Marie-Hélène Mayrand,Jacques Lacroix,Joseph Niyibizi,Louise Laporte,François Audibert,François Coutlée,Helen Trottier,","doi":"10.1093/infdis/jiaf213","DOIUrl":"https://doi.org/10.1093/infdis/jiaf213","url":null,"abstract":"BACKGROUNDLittle is known on the vertical transmission of human papillomavirus (HPV) and on the dynamics of HPV among children. Our objective was to determine the risk of HPV recurrence, persistence, and incidence over 2 years of age among children born to HPV-positive mothers.METHODSWe conducted the HERITAGE study among pregnant women recruited between 2010 and 2016 in Canada. HPV DNA testing was done on vaginal samples collected during the first and third trimesters of pregnancy, and on conjunctival, oral, pharyngeal, and genital samples collected in children from birth and at every 3-6 months up to 2 years. We estimated the probability of HPV vertical transmission, and of HPV recurrence, persistence, and incidence among children during follow-up. Time to clear HPV among children was estimated using Kaplan-Meier technique.RESULTSAmong the 422 women with HPV during pregnancy, 390 carried pregnancy to term, and 395 children were born alive including twins/triplets. HPV vertical transmission was estimated at 7.3% (95% confidence interval [CI], 5.0%-10.4%) with a genotype concordance of 85.2%. During the entire follow-up, we observed 91 HPV detections (among 51 children) including 2 recurrent and 1 persistent. Incident genotypes occurred in 26 of the 270 (9.6%) children with valid HPV testing during follow-up. Most HPV infections detected in children cleared with a mean time of 3.9 months (95% CI, 3.6-4.2 months).CONCLUSIONSHPV vertical transmission and incident HPV occasionally occur during infancy, but the risk of persistence or recurrence is overall very low.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945307","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}

引用次数: 0

Placental Malaria Induces Oxidative Stress in Human Syncytiotrophoblast. 胎盘疟疾诱导人合胞滋养细胞氧化应激。

The Journal of Infectious Diseases Pub Date : 2025-05-14 DOI: 10.1093/infdis/jiaf243

Demba Sarr,Alicer K Andrew,Ashish K Shukla,Stephen Mwalimu,Julie M Moore

{"title":"Placental Malaria Induces Oxidative Stress in Human Syncytiotrophoblast.","authors":"Demba Sarr,Alicer K Andrew,Ashish K Shukla,Stephen Mwalimu,Julie M Moore","doi":"10.1093/infdis/jiaf243","DOIUrl":"https://doi.org/10.1093/infdis/jiaf243","url":null,"abstract":"BACKGROUNDPlacental malaria is characterized by the accumulation of Plasmodium falciparum-infected erythrocytes and maternal inflammation in the intervillous spaces of the placenta. These features are associated with placental damage and fetal compromise. However, understanding of the mechanisms that lead to poor pregnancy outcome and interventions targeting excessive host responses to placental malaria are still lacking. The syncytiotrophoblast, a cell of fetal origin, is known to be responsive to malaria-infected erythrocytes as well as the malaria toxin, hemozoin, but its susceptibility to oxidative stress and how this might contribute to placental damage and dysfunction has not yet been directly investigated.METHODSThe characteristics and key drivers of the syncytiotrophoblast response to oxidative stress were investigated using ex vivo human placental tissues and primary trophoblasts isolated from healthy pregnant women. Primary syncytiotrophoblast was exposed to hemozoin and tumor necrosis factor, a critical inflammatory cytokine, to model conditions found in human placental malaria.RESULTSThe data show remarkable lipid peroxidation in human placental samples from a malaria endemic setting and evidence of a modulated antioxidant response at the transcriptional level. Likewise, primary human syncytiotrophoblast exposed to hemozoin, tumor necrosis factor, and tumor necrosis factor combined with hemozoin in vitro exhibited increased markers of an anti-oxidative response, and, with hemozoin alone, oxidation of lipids and DNA.CONCLUSIONSThese results suggest that oxidative stress in syncytiotrophoblast is promoted by both hemozoin exposure and maternal inflammatory responses to placental malaria and contribute to an increased understanding of placental dysfunction and compromise in this infection.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945422","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}

引用次数: 0

Gastrointestinal Dysmotility, Autonomic Function and Small Intestinal Bacterial Overgrowth among People with Well-Controlled HIV 控制良好的HIV感染者的胃肠运动障碍、自主神经功能和小肠细菌过度生长

The Journal of Infectious Diseases Pub Date : 2025-05-13 DOI: 10.1093/infdis/jiaf238

Jessica Robinson-Papp, Mitali Mehta, Bridget R Mueller, Niyati Neupane, Zhan Zhao, Gabriela Cedillo, Kaitlyn Coyle, Maya Campbell, Mary Catherine George, Emma K T Benn, Gina Lee, Jack Semler

{"title":"Gastrointestinal Dysmotility, Autonomic Function and Small Intestinal Bacterial Overgrowth among People with Well-Controlled HIV","authors":"Jessica Robinson-Papp, Mitali Mehta, Bridget R Mueller, Niyati Neupane, Zhan Zhao, Gabriela Cedillo, Kaitlyn Coyle, Maya Campbell, Mary Catherine George, Emma K T Benn, Gina Lee, Jack Semler","doi":"10.1093/infdis/jiaf238","DOIUrl":"https://doi.org/10.1093/infdis/jiaf238","url":null,"abstract":"Introduction Gastrointestinal dysfunction, including microbiome changes and increased bacterial translocation across a compromised gastrointestinal barrier plays a role in the chronic systemic inflammation experienced by people with HIV (PWH). It is unknown whether autonomic neuropathy (AN) may contribute to these mechanisms by altering gastrointestinal motility. Methods This is a cross-sectional study of 100 PWH and 89 controls. All participants underwent assessment of gastrointestinal transit times using a wireless motility capsule (WMC). All PWH and a subset of controls also underwent: a standardized battery of autonomic function tests summarized as the Modified Composite Autonomic Severity Score (MCASS) and its adrenergic, cardiovagal and sudomotor sub-scores, breath testing for small intestinal bacterial overgrowth (SIBO), and the Patient Assessment of Upper Gastrointestinal Disorders Symptoms (PAGI-SYM) and Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaires. Results Compared to controls, PWH displayed shorter gastric emptying times (GET) and longer small bowel and colonic transit times (SBTT, CTT). Among PWH, GET was associated with PAGI-SYM score. The MCASS and its sudomotor sub-score (reflecting peripheral sympathetic function) were associated with SBTT but not GET or CTT. PWH with prolonged SBTT (&gt;6h) were more likely to have SIBO. Conclusion Gastrointestinal motility is altered in PWH. This study provides preliminary evidence that changes in autonomic function may influence SBTT in PWH and that prolonged SBTT may contribute to the development of SIBO. Future studies are needed to more fully elucidate the pathophysiologic links between HIV-associated AN, altered gastrointestinal motility, the gastrointestinal microbiome, chronic inflammation, and resulting morbidity and mortality among PWH.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940331","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}

引用次数: 0

A case-cluster of aseptic meningitis associated with a newly identified recombinant echovirus6/CoxsackievirusB1 enterovirus 无菌性脑膜炎与新发现的重组echovirus6/柯萨奇病毒b1肠道病毒相关的病例群

The Journal of Infectious Diseases Pub Date : 2025-05-13 DOI: 10.1093/infdis/jiaf247

Kartikeya Cherabuddi, Massimiliano S Tagliamonte, John A Lednicky, David A Ostrov, Tracey L Moquin, Vishal Kaushik Thoomkuntla, Brian Bourgeois, Vidya Sagar Kollu, Nicole M Iovine, Paul D Myers, Kuttichantran Subramaniam, Marco Salemi, J Glenn Morris

{"title":"A case-cluster of aseptic meningitis associated with a newly identified recombinant echovirus6/CoxsackievirusB1 enterovirus","authors":"Kartikeya Cherabuddi, Massimiliano S Tagliamonte, John A Lednicky, David A Ostrov, Tracey L Moquin, Vishal Kaushik Thoomkuntla, Brian Bourgeois, Vidya Sagar Kollu, Nicole M Iovine, Paul D Myers, Kuttichantran Subramaniam, Marco Salemi, J Glenn Morris","doi":"10.1093/infdis/jiaf247","DOIUrl":"https://doi.org/10.1093/infdis/jiaf247","url":null,"abstract":"A daycare teacher presented with complaints of headache, neck stiffness, and fever. Because of initial concerns about meningococcal meningitis, families of daycare attendees were notified and 10 children from the daycare presented for evaluation. CSF from the teacher and nasal swabs from four febrile children were RT-PCR positive for enterovirus. A novel recombinant enterovirus was cultured from the teacher’s CSF and from two of the nasal swabs. The amino-terminal portion of the recombinant virus was derived from an Echovirus E6 with the carboxy-terminal portion originating from a Coxsackievirus B1; recombinant segments were most closely related to similar segments from strains isolated in France. Recombination occurred within the C-2 gene associated with virus replication and virion morphogenesis. Structural modeling predicted that the recombinant protein was capable of forming hexameric and heptameric assemblies. Our data highlight the potential for recombination among enteroviruses, leading to modifications within viral proteins which may impact virulence.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946065","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}

引用次数: 0

Safety, immunogenicity, and protective efficacy in rhesus macaques of a novel recombinant hemagglutinin protein measles virus vaccine. 一种新型重组血凝素蛋白麻疹病毒疫苗的安全性、免疫原性和对恒河猴的保护作用。

The Journal of Infectious Diseases Pub Date : 2025-05-13 DOI: 10.1093/infdis/jiaf244

Jessica H Rubens,Jacqueline K Brockhurst,Shristi Ghimire,Jinjin Wu,Liting Liu,Jason S Villano,Rebecca J Loomis,Alexandrine Derrien-Colemyn,Tracy J Ruckwardt,Barney S Graham,Michael W Watson,Guillaume B E Stewart-Jones,Diane E Griffin

{"title":"Safety, immunogenicity, and protective efficacy in rhesus macaques of a novel recombinant hemagglutinin protein measles virus vaccine.","authors":"Jessica H Rubens,Jacqueline K Brockhurst,Shristi Ghimire,Jinjin Wu,Liting Liu,Jason S Villano,Rebecca J Loomis,Alexandrine Derrien-Colemyn,Tracy J Ruckwardt,Barney S Graham,Michael W Watson,Guillaume B E Stewart-Jones,Diane E Griffin","doi":"10.1093/infdis/jiaf244","DOIUrl":"https://doi.org/10.1093/infdis/jiaf244","url":null,"abstract":"BACKGROUNDMeasles-Mumps-Rubella (MMR) is an effective live-virus vaccine against measles but is poorly immunogenic in infants and contraindicated for pregnant and immunocompromised persons.METHODSWe evaluated immunogenicity and protective efficacy of a novel recombinant dimeric MeV hemagglutinin protein vaccine (rMeV) in rhesus macaques. Macaques (n=4) in four experimental groups were injected at days 0 and 42 with: 1) MMR/MMR; 2) rMeV/rMeV; 3) MMR/rMeV; 4) PBS/PBS and challenged intratracheally with wild type MeV 8-9 months later. Blood, nasopharyngeal (NP), bronchoalveolar lavage (BAL), bone marrow (BM), and lymph nodes (LN) were sampled.RESULTSAll macaques that received a MeV-containing vaccine developed MeV-specific binding and neutralizing antibody titers that were similar at 169 days post-vaccination, regardless of experimental group. After challenge, all unvaccinated macaques had MeV detected in samples of blood, NP, BAL, BM and LN, and one developed a rash. No vaccinated macaque developed a rash or had detectable MeV in PBMC, BM, or NP cells. However, MeV and MeV RNA were detected in BAL samples in all experimental groups with the most virus and longest detection in rMeV-vaccinated animals.CONCLUSIONSImmunization with rMeV protected macaques from rash, viremia and systemic virus spread. Therefore, rMeV is protective against MeV disease and a promising option for patients unable to receive or respond to MMR.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945194","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}

引用次数: 0

Streptococcus pyogenes surveillance through surface swab samples to track the emergence of streptococcal toxic shock syndrome in rural Japan 通过表面拭子样本监测化脓性链球菌以追踪日本农村链球菌中毒性休克综合征的出现

The Journal of Infectious Diseases Pub Date : 2025-05-13 DOI: 10.1093/infdis/jiaf234

Dhammika Leshan Wannigama, Mohan Amarasiri, Phatthranit Phattharapornjaroen, Cameron Hurst, Charin Modchang, Yu Suzuki, Kazunori Moriya, Kazuhiko Miyanaga, Longzhu Cui, Angkana T Huang, Yoshikazu Okuma, Daisuke Akaneya, Junko Igarashi, Mayu Suto, Daisuke Ishizawa, Wakana Imamiya, Ayaka Igarashi, Yoshitaka Shimotai, Andrew C Singer, Naveen Kumar Devanga Ragupathi, Takashi Furukawa, Kazunari Sei, Yangzhong Wang, Talerngsak Kanjanabuch, Paul G Higgins, Nobuhito Nemoto, Aisha Khatib, Anthony Kicic, Sam Trowsdale, Parichart Hongsing, Daisuke Sano, Kenji Shibuya, Shuichi Abe, Hiroshi Hamamoto

引用次数: 0

Estimating Influenza Vaccine Effectiveness Against Laboratory-Confirmed Influenza Using Linked Public Health Information Systems, California, 2023-2024 Season. 使用关联公共卫生信息系统估计流感疫苗对实验室确认流感的有效性，加利福尼亚，2023-2024季节。

The Journal of Infectious Diseases Pub Date : 2025-05-13 DOI: 10.1093/infdis/jiaf248

Sophie Zhu,Joshua Quint,Tomás León,Monica Sun,Nancy J Li,Cynthia Yen,Mark W Tenforde,Brendan Flannery,Seema Jain,Robert Schechter,Cora Hoover,Erin L Murray

{"title":"Estimating Influenza Vaccine Effectiveness Against Laboratory-Confirmed Influenza Using Linked Public Health Information Systems, California, 2023-2024 Season.","authors":"Sophie Zhu,Joshua Quint,Tomás León,Monica Sun,Nancy J Li,Cynthia Yen,Mark W Tenforde,Brendan Flannery,Seema Jain,Robert Schechter,Cora Hoover,Erin L Murray","doi":"10.1093/infdis/jiaf248","DOIUrl":"https://doi.org/10.1093/infdis/jiaf248","url":null,"abstract":"BACKGROUNDMandatory public health reporting of influenza laboratory results and vaccine doses administered in the state of California can provide estimates of seasonal influenza vaccine effectiveness (VE).METHODSWe analyzed linked influenza immunization registry and laboratory reporting data among California residents aged ≥6 months tested for influenza during the 2023-24 influenza season (October 2023-June 2024). Individually linked laboratory reporting included influenza molecular or viral culture test result. Odds Ratios (OR) and 95% confidence intervals (CI) contrasted odds of documented 2023-2024 vaccination among persons with influenza-positive tests versus persons with negative influenza tests. VE was calculated as (1 - adjusted OR) x 100 using logistic regression, adjusting for patient age, race, ethnicity, week of specimen collection, and county of residence.RESULTSAmong 1,382,142 laboratory reports, 129,253 persons (9%) (129,253) had a positive influenza test result, of whom 415,390 (30%) had documented influenza vaccination ≥14 days before test date. VE against laboratory-confirmed influenza was 41% (95% CI, 40%-42%). VE was 32% (95% CI, 31%-33%) against influenza A, 68% (95% CI, 66%-69%) against influenza B, and 26% (95% CI, 24%-29%) among adults aged ≥65 years.CONCLUSIONSInfluenza vaccination was associated with prevention of laboratory-confirmed influenza. Results demonstrated feasibility of assessing seasonal influenza vaccine effectiveness using linked immunization and laboratory data from public health surveillance systems.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945308","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}

引用次数: 0

Increasing Fluconazole Resistance in Candida parapsilosis: A 10-Year Analysis of Blood Culture Isolates at a US Reference Laboratory (2015-2024). 准假丝酵母对氟康唑的耐药性增加：美国参考实验室10年血培养分离株分析（2015-2024）

The Journal of Infectious Diseases Pub Date : 2025-05-13 DOI: 10.1093/infdis/jiaf249

Jack McHugh,Supavit Chesdachai,Murray Dunsirn,Nancy Wengenack,Paschalis Vergidis

引用次数: 0

Cefepime-Taniborbactam-a Novel Combination Therapy for Multidrug-Resistant Pathogens. 头孢吡肟-塔尼波巴坦-一种治疗多重耐药病原体的新型联合疗法。

The Journal of Infectious Diseases Pub Date : 2025-05-12 DOI: 10.1093/infdis/jiaf203

Richard R Watkins,Tracy L Lemonovich,Alejandro J Vila,Robert A Bonomo

{"title":"Cefepime-Taniborbactam-a Novel Combination Therapy for Multidrug-Resistant Pathogens.","authors":"Richard R Watkins,Tracy L Lemonovich,Alejandro J Vila,Robert A Bonomo","doi":"10.1093/infdis/jiaf203","DOIUrl":"https://doi.org/10.1093/infdis/jiaf203","url":null,"abstract":"The ongoing spread of antimicrobial resistance has generated an urgent need for new antibiotics, especially against multidrug-resistant (MDR) gram-negative pathogens. Taniborbactam (previously VNRX-5133) is a novel bicyclic boronate β-lactamase inhibitor with potent, selective, and direct inhibitory activity against Ambler class A, B, C, and D enzymes, including serine and metallo-β-lactamases. Taniborbactam has a broader spectrum of inhibition than any other current β-lactamase inhibitor. The combination of cefepime with taniborbactam is in advanced clinical development. Investigators are studying the activity of cefepime-taniborbactam against gram-negative pathogens, including Enterobacterales species like carbapenem-resistant Klebsiella pneumoniae and MDR Pseudomonas aeruginosa with characterized carbapenem resistance mechanisms. In this review, we discuss the advances in medicinal chemistry that led to the development of cefepime-taniborbactam, the pharmacokinetics and pharmacodynamics, the antimicrobial spectrum of activity, potential uses in the clinic, and mechanisms of resistance. We propose future clinical scenarios to better explore the precise niche of this novel inhibitor combination.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932977","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}

引用次数: 0

Characterization of serotype-specific Dengue virus T cell inhibition 血清型特异性登革病毒T细胞抑制的表征

The Journal of Infectious Diseases Pub Date : 2025-05-08 DOI: 10.1093/infdis/jiaf241

Jinhua Xiang, James H McLinden, Qing Chang, Micaela Fosdick, Hillel Haim, Alexander Ploss, Wesley Hottel, Nirjal Bhattarai, Tomokazu Tamura, Jiayu Zhang, Jon C D Houtman, Jack T Stapleton

{"title":"Characterization of serotype-specific Dengue virus T cell inhibition","authors":"Jinhua Xiang, James H McLinden, Qing Chang, Micaela Fosdick, Hillel Haim, Alexander Ploss, Wesley Hottel, Nirjal Bhattarai, Tomokazu Tamura, Jiayu Zhang, Jon C D Houtman, Jack T Stapleton","doi":"10.1093/infdis/jiaf241","DOIUrl":"https://doi.org/10.1093/infdis/jiaf241","url":null,"abstract":"Background Dengue virus (DENV) serotype -2 and -3 infections are associated with more severe disease outcomes than -1 and -4, though a biological explanation for this has not been identified. Methods DENV serotype effects on human T cell activation were assessed by measuring T cell receptor (TCR)-mediated IL-2 release following TCR stimulation. DENV envelope (env) proteins were expressed in Jurkat CD4+ T cell lines and regions inhibiting TCR inhibition mapped by mutagenesis. TCR-signaling pathway inhibition was characterized by total internal reflection fluorescence microscopy and immunoblot. Reverse genetics validated env mapping results. Results T cell incubation with DENV-1 and -4 inhibited TCR signaling whereas DENV-2 and -3 did not. Inhibition did not require viral replication. DENV env protein expression inhibited TCR by interfering with activation of proximal TCR signaling events. Amino acids (aa’s) 49 to 62 of DENV 1 env were sufficient to inhibit TCR signaling, with env aa’s 55 and 66 being critical. Reverse genetics confirmed that substitution of DENV-2 and -3 aa’s 55 and 66 into DENV-1 and -4 reversed TCR inhibition, and DENV-1 aa 55 and 66 introduced into DENV-2 and -3 enhanced TCR inhibition. Conclusions DENV-2 and -3 are associated with more severe clinical disease than DENV-1 and -4; however, no biological explanation for this difference has been previously identified. We found that DENV-1 and -4 viral particles and env proteins blunt T cell responses by interfering with proximal TCR signaling while DENV-2 and -3 do not, potentially explaining DENV pathogenic outcomes in primary and secondary infection.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"1631 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920252","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}

引用次数: 0