Deficiency of HTR4 and ADRB1 caused by SARS-CoV-2 spike may partially explain multiple COVID-19 related syndromes including depression, cognitive impairment, loss of appetite, heart failure, and hypertension

Lv, Lu; Li, Ang; J, Lu; Zhang, Leiliang

doi:10.1016/j.jinf.2022.11.021

Cited by 5 publications

(3 citation statements)

References 9 publications

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“…Altered expression of genes include CX3CR1 [666], S100A12 [667], CSF2 [668], MPO (myeloperoxidase) [669], CD5L [670], F11 [671], S100A8 [672], PGLYRP1 [673], VEGFD (vascular endothelial growth factor D) [674], CXCL11 [373], BPI (bactericidal permeability increasing protein) [675], CXCL10 [676], S100A9 [677], CXCR1 [678], CXCR2 [679], ABCA3 [680], CD36 [681], SHH (sonic hedgehog signaling molecule) [682], TLR3 [683], CLEC4D [684], CCR2 [685], NEK7 [686], TLR7 [687], CCRL2 [688] and CAV1 [689] accelerates pneumonia progression. CX3CR1 [666], CD177 [690], PF4 [691], FFAR2 [692], MPO (myeloperoxidase) [693], F11 [694], S100A8 [695], VEGFD (vascular endothelial growth factor D) [674], IL1A [696], BPI (bactericidal permeability increasing protein) [697], AQP4 [698], BDNF (brain derived neurotrophic factor) [699], CXCL10 [700], RNASE2 [701], FCGR3B [702], S100A9 [703], IL1B [704], CXCR2 [705], GPIHBP1 [294], CD36 [706], TRIB3 [707], PCSK9 [708], FGF2 [709], FASN (fatty acid synthase) [710], PNPLA3 [711], HSPA6 [712], VIP (vasoactive intestinal peptide) [713], TLR3 [683], ADRB1 [328], SPOCK2 [714], TLR8 [715], CCR2 [716], IFIT3 [717], NEK7 [718], TLR7 [687], EFNB2 [719], CAV1 [720], CR1 [721] and AQP5 [722] plays essential roles in viral respiratory diseases. Previous study confirmed that CX3CR1 [723], S100A12 [724], CD177 [725], PF4 [726], MPO (myeloperoxidase) [727], CD5L [728], F11 […”

Section: Discussionmentioning

confidence: 99%

“…By performing DEGs analysis, 479 up regulated and 479 down regulated DEGs were successfully identified (|logFC| > 0.512 for up regulated genes, |logFC| < -0.831 for down regulated genes and adjust P-value < .05), respectively. Involvement of SLCO1A2 molecule) [315], DACH1 [316], PNPLA3 [317], FGF9 [192], SLC7A11 [193], SGPP1 [318], VIP (vasoactive intestinal peptide) [319], KCNJ2 [320], KL (klotho) [321], SMAD6 [135], BMPR2 [322], APOA1 [323], CALCRL (calcitonin receptor like receptor) [324], INSIG1 [325], RASGRF1 [198], LRRK2 [326], TLR3 [327], ADRB1 [328], SLC22A3 [329], CA2 [330], SNX10 [331], LIFR (LIF receptor subunit alpha) [332], TLR8 [333], CMPK2 [334], GATA3 [335], RSPO2 [336], CCR2 [205], NEK7 [337], TLR7 [338], BEX1 [339], EFNB2 [340], CAV1 [341], ARRB1 [342], TRPC3 [343], CR1 [344], PEG10 [345], DLL4 [346], MEFV (MEFV innate immuity regulator, pyrin) [347], TFPI (tissue factor pathway inhibitor) [348], EPAS1 [349], FADS1 [215], DKK2 [350], CACNA2D2 [351], DPP6 [352]…”

Section: Discussionmentioning

confidence: 99%

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Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2023

Preprint

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Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with reduced quality of life and earlier mortality, but its pathogenesis and key genes are still unclear. In this investigation, bioinformatics was used to deeply analyze the pathogenesis of IPF and related key genes, so as to investigate the potential molecular pathogenesis of IPF and provide guidance for clinical treatment. Next generation sequencing dataset GSE213001 was obtained from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were identified between IPF and normal control group. The DEGs between IPF and normal control group were screened with the DESeq2 package of R language. The Gene Ontology (GO) and REACTOME pathway enrichment analyses of the DEGs were performed. Using the g:Profiler, the function and pathway enrichment analysis of DEGs were performed. Then, a protein protein interaction (PPI) network was constructed via the Integrated Interactions Database (IID) database. Cytoscape with Network Analyzer was used to identify the hub genes. miRNet and NetworkAnalyst database was used to construct the targeted microRNAs (miRNAs) and transcription factors (TFs) of the hub genes. Finally receiver operating characteristic (ROC) curve analysis was used to validates the hub genes. A total of 958 DEGs were screened out in this study, including 479 up regulated genes and 479 down regulated genes. Most of the DEGs were significantly enriched in response to stimulus, GPCR ligand binding, microtubule-based process and defective GALNT3 causes HFTC. In combination with the results of the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network, hub genes including LRRK2, BMI1, EBP, MNDA, KBTBD7, KRT15, OTX1, TEKT4, SPAG8 and EFHC2 were selected. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of IPF, and provide a novel strategy for clinical therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2023

Preprint

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“…Recently, the endocytic recycling of angiotensin converting enzyme 2 (ACE2), glucose transporter type 1 (GLUT1), hydroxytryptamine receptor 4 (HTR4) and adrenoceptor beta 1 (ADRB1) was inhibited by SARS-CoV-2 S, possibly explaining some COVID symptoms associated with deficiency of those surface proteins. (Ren et al, 2022a;Ren et al, 2022b;Lv et al, 2023) The underlying mechanisms are that the spike (S) protein from SARS-CoV-2 binds to SNX27's PDZ domain and reduces the association between SNX27 and Vps26A. (Ren et al, 2022a;Ren et al, 2022b) Since ATP7A is also a cargo of SNX27 in the recycling pathway, (Steinberg et al, 2013) SARS-CoV-2 S protein may suppress ATP7A recycling to the cell surface by associating with SNX27.…”

Section: Conclusion and Prospectmentioning

confidence: 99%

The interplay between copper metabolism and microbes: in perspective of host copper-dependent ATPases ATP7A/B

Zhou,

Zhang

2023

Front. Cell. Infect. Microbiol.

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Copper, a vital element in various physiological processes, is transported from the gastrointestinal tract to tissues and cells through diverse copper transporters. Among these transporters, ATP7A and ATP7B play significant roles in regulating systemic copper metabolism and exhibit precise regulation in their intracellular trafficking. These transporters undergo dynamic shuttling between the trans-Golgi network (TGN) and the plasma membrane via the endocytic recycling mechanism, which involves the retromer and other associated factors. Interestingly, the antimicrobial attribute of copper implies a potential connection between microbial infection and copper metabolism. Several microbes, including Salmonella enterica, Cryptococcus, Influenza A virus (IAV) and Zika virus (ZIKV) have been observed to impact the regulatory mechanisms of ATP7A/B, either directly or indirectly, as a means of survival. This review summarizes the key features and trafficking mechanisms of the copper transporters ATP7A/B, and examines the intricate interplay between microbes and copper metabolism. Ultimately, it highlights how microbes can perturb copper homeostasis through interactions with host factors, offering valuable insights into the mechanistic aspects of host-microbe interactions.

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The risk of future mpox outbreaks among men who have sex with men: a modelling study based on cross-sectional seroprevalence data

Shamier,

Zaeck,

Götz

et al. 2023

Preprint

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SummaryBackgroundIn the wake of the 2022-2023 mpox outbreak, crucial knowledge gaps exist regarding orthopoxvirus-specific immunity in risk groups and its impact on future outbreaks. Here, we combined cross-sectional seroprevalence studies in two cities in the Netherlands with mathematical modelling to evaluate the risk of future mpox outbreaks among men who have sex with men (MSM).MethodsSerum samples were obtained from 1,065 MSM visiting the Centres for Sexual Health (CSH) in Rotterdam or Amsterdam after the introduction of vaccination and the peak of the Dutch mpox outbreak. For MSM visiting the CSH in Rotterdam, sera were linked to epidemiological and vaccination data. An in-house developed ELISA was used to detect vaccinia virus (VACV)- specific IgG; plaque reduction neutralization tests (PRNT) were performed on a selection of samples. These observations were combined with literature data on infection dynamics and vaccine effectiveness to inform a stochastic transmission model to estimate the risk on future mpox outbreaks.FindingsThe seroprevalence of VACV-specific IgG was 45.4% and 47.1% in Rotterdam and Amsterdam, respectively. Based on the correlation between serological parameters, we identified confirmed MPXV infections and inferred nine undiagnosed infections in individuals without childhood smallpox vaccination in the Rotterdam cohort (5.1%). Transmission modelling showed that the overall number of mpox cases in new outbreaks would be low, but that the current level of immunity alone may not prevent future outbreaks. Maintaining a short time-to-diagnosis will be a key component of any strategy to prevent new outbreaks.InterpretationOur findings indicate a reduced likelihood of future mpox outbreaks among MSM in the Netherlands under the current conditions, but emphasise the importance of maintaining population immunity, diagnostic capacities, and disease awareness.FundingNational Institute for Public Health and the Environment (RIVM), HORIZON-HLTH-2022-MPX-14 (101115188).Research in contextEvidence before this studyWe searched PubMed from database inception to July 24th, 2023, using the search terms (“monkeypox” OR “mpox” OR “orthopoxvirus”) AND (“immunity” OR “antibodies” OR vaccin*) OR (model*) OR (“epidemiology” OR “outbreak”) OR (“seroprevalence” OR “serosurveillance”), with no date or language restrictions. We included the cited references of retrieved publications in our search. We found that there are crucial knowledge gaps with respect to monkeypox virus (MPXV)-specific immunity and the impact of risk group vaccination with third-generation smallpox vaccines on the prevention of future outbreaks. No seroprevalence studies following the 2022-2023 mpox outbreak have been published yet. Recent observational studies from Israel, the United Kingdom, and the United States reported adjusted vaccine effectiveness levels between 36% - 86% following one or two doses of MVA. After the massive 2022-2023 outbreak, the number of new cases is now at a very low level, although there are continouing reports of small clusters of infections, including breakthrough infections and re-infections. This long tail to the epi curve, raises concerns about the potential of future outbreaks. We found no studies that predicted the risk of future mpox outbreaks after risk group vaccination based on measured seroprevalence data.Added value of this studyThe primary goal of this study was to estimate the risk of future mpox outbreaks among men who have sex with men (MSM) in the Netherlands using mathematical modelling based on real-world data. To this end, we used a combination of serological assays to determine the presence and abundance of (functional) poxvirus-specific antibodies in a Dutch MSM cohort. Next, we demonstrate the impact of rapid diagnosis (followed by isolation) of mpox cases on the size and duration of future outbreaks employing a mathematical model.Implications of all the available evidenceA seroprevalence level of approximately 45% among MSM in the Netherlands visiting the Centres for Sexual Health was found. Modelling showed that this seroprevalence level alone may not be sufficient to prevent future outbreaks, which emphasises the importance of continued disease awareness, and maintaining population immunity and diagnostic capacities. These insights have important implications for public health policy making and fill critical knowledge gaps to help inform surveillance activities and guide vaccination strategies.

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Deficiency of HTR4 and ADRB1 caused by SARS-CoV-2 spike may partially explain multiple COVID-19 related syndromes including depression, cognitive impairment, loss of appetite, heart failure, and hypertension

Cited by 5 publications

References 9 publications

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

The interplay between copper metabolism and microbes: in perspective of host copper-dependent ATPases ATP7A/B

The risk of future mpox outbreaks among men who have sex with men: a modelling study based on cross-sectional seroprevalence data

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