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Browsing by Subject "Viral infection"

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    A rare presentation of herpes simplex virus encephalitis occurring in a pediatric patient on dupilumab for atopic dermatitis
    (Wiley, 2022) Rao, Megana; Grove, Daniel; Haggstrom, Anita; Medicine, School of Medicine
    A 4‐year‐old female with a history of atopic dermatitis developed herpes simplex virus (HSV) encephalitis while being treated with dupilumab and concomitant topical steroids. There was no prior history of HSV infections or immunodeficiency. To our knowledge, this is the first case of HSV encephalitis in a patient receiving dupilumab.
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    Adverse events following administration of COVID-19 vaccines in Saudi Arabia
    (Springer Nature, 2022-11-15) Alqahtani, Saleh; Jokhdar, Hani; Al‑Tawfiq, Jaffar A.; Al‑Otaibi, Salah; Assiri, Abdullah; Almudarra, Sami; Alabdulkareem, Khaled; Haji, Alhan; Medicine, School of Medicine
    Previous studies investigated the frequency of different adverse events of COVID-19 vaccines. However, this study compares these adverse events between the two main COVID-19 vaccines used in Saudi Arabia (Pfizer-BioNTech and Oxford-AstraZeneca) using telemedicine technology. A cross-sectional study was conducted among 958 individuals, 7 days after receiving either Pfizer-BioNTech or Oxford-AstraZeneca vaccines during June 2021. Immediate adverse events were reported by 1.04% and 2.09% for Pfizer-BioNTech and Oxford-AstraZeneca vaccines, respectively, with no serious events. Recipients of Pfizer-BioNTech vaccine had a higher percentage of local adverse events (24.8% versus 9.8% in AstraZeneca vaccine). The most common reported systemic adverse events in both vaccines respectively were general fatigue (23.1% and 25.1%), fever (18.5% and 27.2%), myalgia (20.6% and 20.3%), and headache (15.2% and 17.2%). No significant difference was recorded between both vaccines regarding overall systemic adverse events; however, they were more frequent following the first dose of AstraZeneca vaccine compared to Pfizer-BioNTech vaccine, while the reverse was observed for the second dose. Adverse events were more frequent in females and younger age groups for both vaccines. Most of systemic and local adverse events were mild in nature. Further cohort studies are recommended to investigate the long-term adverse events of COVID-19 vaccines.
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    Author Correction: Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C
    (Springer Nature, 2022-08-12) Tang, Juanjie; Novak, Tanya; Hecker, Julian; Grubbs, Gabrielle; Zahra, Fatema Tuz; Bellusci, Lorenza; Pourhashemi, Sara; Chou, Janet; Moffitt, Kristin; Halasa, Natasha B.; Schwartz, Stephanie P.; Walker, Tracie C.; Tarquinio, Keiko M.; Zinter, Matt S.; Staat, Mary A.; Gertz, Shira J.; Cvijanovich, Natalie Z.; Schuster, Jennifer E.; Loftis, Laura L.; Coates, Bria M.; Mack, Elizabeth H.; Irby, Katherine; Fitzgerald, Julie C.; Rowan, Courtney M.; Kong, Michele; Flori, Heidi R.; Maddux, Aline B.; Shein, Steven L.; Crandall, Hillary; Hume, Janet R.; Hobbs, Charlotte V.; Tremoulet, Adriana H.; Shimizu, Chisato; Burns, Jane C.; Chen, Sabrina R.; Moon, Hye Kyung; Lange, Christoph; Randolph, Adrienne G.; Khurana, Surender; Pediatrics, School of Medicine
    Correction to: Nature Communications 10.1038/s41467-022-30649-1, published online 27 May 2022
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    Autophagy in liver diseases: A matter of what to remove and whether to keep
    (KeAi Communications, 2018-09) Yin, Xiao-Ming; Pathology and Laboratory Medicine, School of Medicine
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    The butterfly effect in viral infection: From a host DNA single nucleotide change to HBV episome steadiness
    (Elsevier, 2019-02-10) Kim, Elena S.; Guo, Haitao; Microbiology and Immunology, School of Medicine
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    Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C
    (Springer Nature, 2022-05-27) Tang, Juanjie; Novak, Tanya; Hecker, Julian; Grubbs, Gabrielle; Tuz Zahra, Fatema; Bellusci, Lorenza; Pourhashemi, Sara; Chou, Janet; Moffitt, Kristin; Halasa, Natasha B.; Schwartz, Stephanie P.; Walker, Tracie C.; Tarquinio, Keiko M.; Zinter, Matt S.; Staat, Mary A.; Gertz, Shira J.; Cvijanovich, Natalie Z.; Schuster, Jennifer E.; Loftis, Laura L.; Coates, Bria M.; Mack, Elizabeth H.; Irby, Katherine; Fitzgerald, Julie C.; Rowan, Courtney M.; Kong, Michele; Flori, Heidi R.; Maddux, Aline B.; Shein, Steven L.; Crandall, Hillary; Hume, Janet R.; Hobbs, Charlotte V.; Tremoulet, Adriana H.; Shimizu, Chisato; Burns, Jane C.; Chen, Sabrina R.; Moon, Hye Kyung; Lange, Christoph; Randolph, Adrienne G.; Khurana, Surender; Pediatrics, School of Medicine
    Neutralization capacity of antibodies against Omicron after a prior SARS-CoV-2 infection in children and adolescents is not well studied. Therefore, we evaluated virus-neutralizing capacity against SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants by age-stratified analyses (<5, 5-11, 12-21 years) in 177 pediatric patients hospitalized with severe acute COVID-19, acute MIS-C, and in convalescent samples of outpatients with mild COVID-19 during 2020 and early 2021. Across all patients, less than 10% show neutralizing antibody titers against Omicron. Children <5 years of age hospitalized with severe acute COVID-19 have lower neutralizing antibodies to SARS-CoV-2 variants compared with patients >5 years of age. As expected, convalescent pediatric COVID-19 and MIS-C cohorts demonstrate higher neutralization titers than hospitalized acute COVID-19 patients. Overall, children and adolescents show some loss of cross-neutralization against all variants, with the most pronounced loss against Omicron. In contrast to SARS-CoV-2 infection, children vaccinated twice demonstrated higher titers against Alpha, Beta, Gamma, Delta and Omicron. These findings can influence transmission, re-infection and the clinical disease outcome from emerging SARS-CoV-2 variants and supports the need for vaccination in children.
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    Decoding the immune dance: Unraveling the interplay between beta cells and type 1 diabetes
    (Elsevier, 2024) Roy, Saptarshi; Pokharel, Pravil; Piganelli, Jon D.; Medicine, School of Medicine
    Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by the specific destruction of insulin-producing beta cells in the pancreas by the immune system, including CD4 cells which orchestrate the attack and CD8 cells which directly destroy the beta cells, resulting in the loss of glucose homeostasis. Scope of review: This comprehensive document delves into the complex interplay between the immune system and beta cells, aiming to shed light on the mechanisms driving their destruction in T1D. Insights into the genetic predisposition, environmental triggers, and autoimmune responses provide a foundation for understanding the autoimmune attack on beta cells. From the role of viral infections as potential triggers to the inflammatory response of beta cells, an intricate puzzle starts to unfold. This exploration highlights the importance of beta cells in breaking immune tolerance and the factors contributing to their targeted destruction. Furthermore, it examines the potential role of autophagy and the impact of cytokine signaling on beta cell function and survival. Major conclusions: This review collectively represents current research findings on T1D which offers valuable perspectives on novel therapeutic approaches for preserving beta cell mass, restoring immune tolerance, and ultimately preventing or halting the progression of T1D. By unraveling the complex dynamics between the immune system and beta cells, we inch closer to a comprehensive understanding of T1D pathogenesis, paving the way for more effective treatments and ultimately a cure.
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    An epidemic Zika virus isolate suppresses antiviral immunity by disrupting antigen presentation pathways
    (Springer Nature, 2021-06-30) Pardy, Ryan D.; Valbon, Stefanie F.; Cordeiro, Brendan; Krawczyk, Connie M.; Richer, Martin J.; Microbiology and Immunology, School of Medicine
    Zika virus (ZIKV) has emerged as an important global health threat, with the recently acquired capacity to cause severe neurological symptoms and to persist within host tissues. We previously demonstrated that an early Asian lineage ZIKV isolate induces a highly activated CD8 T cell response specific for an immunodominant epitope in the ZIKV envelope protein in wild-type mice. Here we show that a contemporary ZIKV isolate from the Brazilian outbreak severely limits CD8 T cell immunity in mice and blocks generation of the immunodominant CD8 T cell response. This is associated with a more sustained infection that is cleared between 7- and 14-days post-infection. Mechanistically, we demonstrate that infection with the Brazilian ZIKV isolate reduces the cross-presentation capacity of dendritic cells and fails to fully activate the immunoproteasome. Thus, our study provides an isolate-specific mechanism of host immune evasion by one Brazilian ZIKV isolate, which differs from the early Asian lineage isolate and provides potential insight into viral persistence associated with recent ZIKV outbreaks.
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    A functional requirement for sex-determination M/m locus region lncRNA genes in Aedes aegypti female larvae
    (Springer Nature, 2021-05-20) Mysore, Keshava; Hapairai, Limb K.; Li, Ping; Roethele, Joseph B.; Sun, Longhua; Igiede, Jessica; Misenti, Joi K.; Duman‑Scheel, Molly; Medical and Molecular Genetics, School of Medicine
    Although many putative long non-coding RNA (lncRNA) genes have been identified in insect genomes, few of these genes have been functionally validated. A screen for female-specific larvicides that facilitate Aedes aegypti male sex separation uncovered multiple interfering RNAs with target sites in lncRNA genes located in the M/m locus region, including loci within or tightly linked to the sex determination locus. Larval consumption of a Saccharomyces cerevisiae (yeast) strain engineered to express interfering RNA corresponding to lncRNA transcripts resulted in significant female death, yet had no impact on male survival or fitness. Incorporation of the yeast larvicides into mass culturing protocols facilitated scaled production and separation of fit adult males, indicating that yeast larvicides could benefit mosquito population control strategies that rely on mass releases of male mosquitoes. These studies functionally verified a female-specific developmental requirement for M/m locus region lncRNA genes, suggesting that sexually antagonistic lncRNA genes found within this highly repetitive pericentromeric DNA sequence may be contributing to the evolution of A. aegypti sex chromosomes.
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    IFN-α Induces Heterogenous ROS Production in Human β-Cells
    (bioRxiv, 2025-02-20) Wagner, Leslie E.; Melnyk, Olha; Turner, Abigail; Duffett, Bryce E.; Muralidharan, Charanya; Martinez-Irizarry, Michelle M.; Arvin, Matthew C.; Orr, Kara S.; Manduchi, Elisabetta; Kaestner, Klaus H.; Brozinick, Joseph T.; Linnemann, Amelia K.; Biochemistry and Molecular Biology, School of Medicine
    Type 1 diabetes (T1D) is a multifactorial disease involving genetic and environmental factors, including viral infection. We investigated the impact of interferon alpha (IFN-α), a cytokine produced during the immune response to viral infection or the presence of un-edited endogenous double-stranded RNAs, on human β-cell physiology. Intravital microscopy on transplanted human islets using a β-cell-selective reactive oxygen species (ROS) biosensor (RIP1-GRX1-roGFP2), revealed a subset of human β-cells that acutely produce ROS in response to IFN-α. Comparison to Integrated Islet Distribution Program (IIDP) phenotypic data revealed that healthier donors had more ROS accumulating cells. In vitro IFN-α treatment of human islets similarly elicited a heterogenous increase in superoxide production that originated in the mitochondria. To determine the unique molecular signature predisposing cells to IFN-α stimulated ROS production, we flow sorted human islets treated with IFN-α. RNA sequencing identified genes involved in inflammatory and immune response in the ROS-producing cells. Comparison with single cell RNA-Seq datasets available through the Human Pancreas Analysis Program (HPAP) showed that genes upregulated in ROS-producing cells are enriched in control β-cells rather than T1D donors. Combined, these data suggest that IFN-α stimulates mitochondrial ROS production in healthy human β-cells, potentially predicting a more efficient antiviral response.
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