Inhibition of EV71 replication by an interferon-stimulated gene product L3HYPDH

Liu, Jian; Liu, Logen; Zeng, Shinuan; Meng, Xiaobin; Lei, Nanfeng; Yang, Hai; Li, Runcai; Mu, Xin; Guo, Xuemin

doi:10.1016/j.virusres.2024.199336

Cited by 2 publications

(1 citation statement)

References 34 publications

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“…In the last few decades, EV71 has gradually become a significant threat to human health throughout the world, especially in Australia, Singapore, Japan, China, Malaysia, and other countries of Asia-Pacific, resulting in hospitalization and mortality rates ranging from 5% to 19% in children [7][8][9][10]. Most studies to date have focused on the identification of novel host factors, the IFN-mediated antiviral response, the discovery or development of effective antivirals, and the elucidation of host-pathogen interactions during EV71 infection [3,[11][12][13]. For example, EV71 (2Apro) has been found to upregulate the expression and secretion of LDL-receptor-related protein-associated protein 1 (LRPAP1), and the N-terminus of secreted LRPAP1 can bind with the extracellular domain of IFNAR1, triggering the receptor's ubiquitination and degradation and promoting virus infection both in vitro and in vivo [14].…”

Section: Introductionmentioning

confidence: 99%

Scorpion Venom Antimicrobial Peptide Derivative BmKn2-T5 Inhibits Enterovirus 71 in the Early Stages of the Viral Life Cycle In Vitro

Xia,

Wang,

Chen

et al. 2024

Biomolecules

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Enterovirus 71 (EV71), a typical representative of unenveloped RNA viruses, is the main pathogenic factor responsible for hand, foot, and mouth disease (HFMD) in infants. This disease seriously threatens the health and lives of humans worldwide, especially in the Asia–Pacific region. Numerous animal antimicrobial peptides have been found with protective functions against viruses, bacteria, fungi, parasites, and other pathogens, but there are few studies on the use of scorpion-derived antimicrobial peptides against unenveloped viruses. Here, we investigated the antiviral activities of scorpion venom antimicrobial peptide BmKn2 and five derivatives, finding that BmKn2 and its derivative BmKn2-T5 exhibit a significant inhibitory effect on EV71. Although both peptides exhibit characteristics typical of amphiphilic α-helices in terms of their secondary structure, BmKn2-T5 displayed lower cellular cytotoxicity than BmKn2. BmKn2-T5 was further found to inhibit EV71 in a dose-dependent manner in vitro. Moreover, time-of-drug-addition experiments showed that BmKn2-T5 mainly restricts EV71, but not its virion or replication, at the early stages of the viral cycle. Interestingly, BmKn2-T5 was also found to suppress the replication of the enveloped viruses DENV, ZIKV, and HSV-1 in the early stages of the viral cycle, which suggests they may share a common early infection step with EV71. Together, the results of our study identified that the scorpion-derived antimicrobial peptide BmKn2-T5 showed valuable antiviral properties against EV71 in vitro, but also against other enveloped viruses, making it a potential new candidate therapeutic molecule.

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Section: Introductionmentioning

confidence: 99%

Scorpion Venom Antimicrobial Peptide Derivative BmKn2-T5 Inhibits Enterovirus 71 in the Early Stages of the Viral Life Cycle In Vitro

Xia,

Wang,

Chen

et al. 2024

Biomolecules

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A transcriptome-wide Mendelian randomization study in isolated human immune cells highlights risk genes involved in viral infections and potential drug repurposing opportunities for schizophrenia

Stacey,

Gaziano,

Eldi

et al. 2024

Preprint

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BackgroundSchizophrenia is a neurodevelopmental psychiatric disorder characterised by symptoms of psychosis, thought disorder, and flattened affect. Immune mechanisms are associated with schizophrenia, though the precise nature of this relationship (i.e., causal, correlated, consequential) and the mechanisms involved are not fully understood.MethodsTo elucidate these mechanisms, we conducted a transcriptome-wide Mendelian randomization study using gene expression exposures from 29 humancis-eQTL datasets encompassing 11 unique immune cell types, all publicly available from the eQTL catalogue.ResultsThese analyses highlighted 196 genes, including 67 located within the human leukocyte antigen (HLA) region. Enrichment analyses indicated an over-representation of immune genes, which was driven by the HLA genes. Stringent validation and replication steps retained 61 candidate genes, 27 of which were the sole causal signals at their respective loci, thereby representing strong candidate effector genes at known risk loci. We highlightedL3HYPDHas a potential novel schizophrenia risk gene andDPYDandMAPK3as candidate drug repurposing targets. Futhermore, we performed follow-up analyses focused on one of the candidate effectors, interferon regulatory transcription factor 3 (IRF3), which coordinates interferon responses to viral infections. We found evidence of shared genetic aetiology between schizophrenia and autoimmune diseases at theIRF3locus, and a significant enrichment of IRF3 chromatin binding at known schizophrenia risk loci.ConclusionsOur findings highlight a novel schizophrenia risk gene, potential drug repurposing opportunities, and provide support forIRF3as a schizophrenia hub gene, which may play critical roles in mediating schizophrenia-autoimmune comorbidities and the impact of viral infections on schizophrenia risk.

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Inhibition of EV71 replication by an interferon-stimulated gene product L3HYPDH

Cited by 2 publications

References 34 publications

Scorpion Venom Antimicrobial Peptide Derivative BmKn2-T5 Inhibits Enterovirus 71 in the Early Stages of the Viral Life Cycle In Vitro

Scorpion Venom Antimicrobial Peptide Derivative BmKn2-T5 Inhibits Enterovirus 71 in the Early Stages of the Viral Life Cycle In Vitro

A transcriptome-wide Mendelian randomization study in isolated human immune cells highlights risk genes involved in viral infections and potential drug repurposing opportunities for schizophrenia

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