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Article ; Online: Corrigendum to "Immune evasion of neutralizing antibodies by SARS-CoV-2 Omicron" [Cytokine Growth Factor Rev. 70 (2023) 13-25].

Wang, Lidong / Møhlenberg, Michelle / Wang, Pengfei / Zhou, Hao

2024

Language	English
Publishing date	2024-04-12
Publishing country	England
Document type	Published Erratum
ZDB-ID	1330534-7
ISSN	1879-0305 ; 1359-6101
ISSN (online)	1879-0305
ISSN	1359-6101
DOI	10.1016/j.cytogfr.2024.03.006
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Article ; Online: SARS-CoV-2 surveillance in medical and industrial wastewater-a global perspective: a narrative review.

Yang, Kaiwen / Guo, Jinlin / Møhlenberg, Michelle / Zhou, Hao

Environmental science and pollution research international

2023 Volume 30, Issue 23, Page(s) 63323–63334

Abstract: The novel coronavirus SARS-CoV-2 has spread at an unprecedented rate since late 2019, leading to the global COVID-19 pandemic. During the pandemic, being able to detect SARS-CoV-2 in human populations with high coverage quickly is a huge challenge. As ... ...

Abstract	The novel coronavirus SARS-CoV-2 has spread at an unprecedented rate since late 2019, leading to the global COVID-19 pandemic. During the pandemic, being able to detect SARS-CoV-2 in human populations with high coverage quickly is a huge challenge. As SARS-CoV-2 is excreted in human excreta and thus exposed to the aqueous environment through sewers, the goal is to develop an ideal, non-invasive, cost-effective epidemiological method for detecting SARS-CoV-2. Wastewater surveillance has gained widespread interest and is increasingly being investigated as an effective early warning tool for monitoring the spread and evolution of the virus. This review emphasizes important findings on SARS-CoV-2 wastewater-based epidemiology (WBE) in different continents and techniques used to detect SARS-CoV-2 in wastewater during the period 2020-2022. The results show that WBE is a valuable population-level method for monitoring SARS-CoV-2 and is a valuable early warning alert. It can assist policymakers in formulating relevant policies to avoid the negative impacts of early or delayed action. Such strategy can also help avoid unnecessary wastage of medical resources, rationalize vaccine distribution, assist early detection, and contain large-scale outbreaks.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19/epidemiology ; Wastewater ; Pandemics ; Wastewater-Based Epidemiological Monitoring
Chemical Substances	Wastewater
Language	English
Publishing date	2023-03-29
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1178791-0
ISSN	1614-7499 ; 0944-1344
ISSN (online)	1614-7499
ISSN	0944-1344
DOI	10.1007/s11356-023-26571-8
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Article ; Online: Immune evasion of neutralizing antibodies by SARS-CoV-2 Omicron.

Wang, Lidong / Møhlenberg, Michelle / Wang, Pengfei / Zhou, Hao

Cytokine & growth factor reviews

2023 Volume 70, Page(s) 13–25

Abstract: Since its emergence at the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the infection of more than 600 million people worldwide and has significant damage to global medical, economic, and political structures. ... ...

Abstract	Since its emergence at the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the infection of more than 600 million people worldwide and has significant damage to global medical, economic, and political structures. Currently, a highly mutated variant of concern, SARS-CoV-2 Omicron, has evolved into many different subvariants mainly including BA.1, BA.2, BA.3, BA.4/5, and the recently emerging BA.2.75.2, BA.2.76, BA.4.6, BA.4.7, BA.5.9, BF.7, BQ.1, BQ.1.1, XBB, XBB.1, etc. Mutations in the N-terminal domain (NTD) of the spike protein, such as A67V, G142D, and N212I, alter the antigenic structure of Omicron, while mutations in the spike receptor binding domain (RBD), such as R346K, Q493R, and N501Y, increase the affinity for angiotensin-converting enzyme 2 (ACE2). Both types of mutations greatly increase the capacity of Omicron to evade immunity from neutralizing antibodies, produced by natural infection and/or vaccination. In this review, we systematically assess the immune evasion capacity of SARS-CoV-2, with an emphasis on the neutralizing antibodies generated by different vaccination regimes. Understanding the host antibody response and the evasion strategies employed by SARS-CoV-2 variants will improve our capacity to combat newly emerging Omicron variants.
MeSH term(s)	Humans ; Antibodies, Neutralizing ; SARS-CoV-2/genetics ; Immune Evasion ; COVID-19
Chemical Substances	Antibodies, Neutralizing
Language	English
Publishing date	2023-03-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1330534-7
ISSN	1879-0305 ; 1359-6101
ISSN (online)	1879-0305
ISSN	1359-6101
DOI	10.1016/j.cytogfr.2023.03.001
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Article ; Online: The role of IFNL4 in liver inflammation and progression of fibrosis.

Møhlenberg, Michelle / O'Brien, Thomas R / Hartmann, Rune

Genes and immunity

2022 Volume 23, Issue 3-4, Page(s) 111–117

Abstract: The discovery that genetic variation within the interferon lambda locus has a profound effect on the outcome of hepatitis C virus (HCV) treatment and spontaneous clearance of HCV is one of the great triumphs of genomic medicine. Subsequently, the IFNL4 ... ...

Abstract	The discovery that genetic variation within the interferon lambda locus has a profound effect on the outcome of hepatitis C virus (HCV) treatment and spontaneous clearance of HCV is one of the great triumphs of genomic medicine. Subsequently, the IFNL4 gene was discovered and proposed as the causal gene underlying this association. However, there has been a lively debate within the field concerning the causality, which has been further complicated by a change in naming. This review summarizes the genetic data available for the IFNL3/IFNl4 loci and provides an in-depth discussion of causality. We also discuss a new series of interesting data suggesting that the genetic variation at the IFNL4 loci influences the evolution of the HCV virus and the implication this relationship between our genetic makeup and virus evolution has upon our understanding of the IFNL4 system. Finally, new data support an influence of the IFNL4 gene upon liver inflammation and fibrosis that is independent of etiology, thereby linking the IFNL4 gene to some of the major liver diseases of today.
MeSH term(s)	Fibrosis ; Genotype ; Hepacivirus ; Hepatitis C/genetics ; Humans ; Inflammation/genetics ; Interferons/genetics ; Interleukins/genetics ; Polymorphism, Single Nucleotide
Chemical Substances	IFNL4 protein, human ; Interleukins ; Interferons (9008-11-1)
Language	English
Publishing date	2022-05-18
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Intramural
ZDB-ID	2060566-3
ISSN	1476-5470 ; 1466-4879
ISSN (online)	1476-5470
ISSN	1466-4879
DOI	10.1038/s41435-022-00173-9
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Article ; Online: The Influence of the rs30461 Single Nucleotide Polymorphism on IFN-λ1 Activity and Secretion.

Møhlenberg, Michelle / Gad, Hans Henrik / Hartmann, Rune

Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

2019 Volume 39, Issue 10, Page(s) 661–667

Abstract: Genetic variation within ... ...

Abstract	Genetic variation within the
MeSH term(s)	Hep G2 Cells ; Humans ; Interferons/genetics ; Interferons/metabolism ; Interleukins/genetics ; Interleukins/metabolism ; Polymorphism, Single Nucleotide
Chemical Substances	interferon-lambda, human ; Interleukins ; Interferons (9008-11-1)
Language	English
Publishing date	2019-05-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1226675-9
ISSN	1557-7465 ; 1079-9907
ISSN (online)	1557-7465
ISSN	1079-9907
DOI	10.1089/jir.2019.0051
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Article ; Online: Impaired STING Activation Due to a Variant in the E3 Ubiquitin Ligase AMFR in a Patient with Severe VZV Infection and Hemophagocytic Lymphohistiocytosis.

Thomsen, Michelle Mølgaard / Skouboe, Morten Kelder / Møhlenberg, Michelle / Zhao, Jian / de Keukeleere, Kerstin / Heinz, Johanna Laura / Werner, Marvin / Hollensen, Anne Kruse / Lønskov, Jonas / Nielsen, Ian / Carter-Timofte, Madalina Elena / Zhang, Baocun / Mikkelsen, Jacob Giehm / Fisker, Niels / Paludan, Søren R / Assing, Kristian / Mogensen, Trine H

Journal of clinical immunology

2024 Volume 44, Issue 2, Page(s) 56

Abstract: Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus exclusively infecting humans, causing two distinct pathologies: varicella (chickenpox) upon primary infection and herpes zoster (shingles) following reactivation. In susceptible individuals, ... ...

Abstract	Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus exclusively infecting humans, causing two distinct pathologies: varicella (chickenpox) upon primary infection and herpes zoster (shingles) following reactivation. In susceptible individuals, VZV can give rise to more severe clinical manifestations, including disseminated infection, pneumonitis, encephalitis, and vasculopathy with stroke. Here, we describe a 3-year-old boy in whom varicella followed a complicated course with thrombocytopenia, hemorrhagic and necrotic lesions, pneumonitis, and intermittent encephalopathy. Hemophagocytic lymphohistiocytosis (HLH) was strongly suspected and as the condition deteriorated, HLH therapy was initiated. Although the clinical condition improved, longstanding hemophagocytosis followed despite therapy. We found that the patient carries a rare monoallelic variant in autocrine motility factor receptor (AMFR), encoding a ubiquitin ligase involved in innate cytosolic DNA sensing and interferon (IFN) production through the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway. Peripheral blood mononuclear cells (PBMCs) from the patient exhibited impaired signaling downstream of STING in response dsDNA and 2'3'-cGAMP, agonists of cGAS and STING, respectively, and fibroblasts from the patient showed impaired type I IFN responses and significantly increased VZV replication. Overexpression of the variant AMFR R594C resulted in decreased K27-linked STING ubiquitination compared to WT AMFR. Moreover, ImageStream technology revealed reduced STING trafficking from ER to Golgi in cells expressing the patient AMFR R594C variant. This was supported by a dose-dependent dominant negative effect of expression of the patient AMFR variant as measured by IFN-β reporter gene assay. Finally, lentiviral transduction with WT AMFR partially reconstituted 2'3'-cGAMP-induced STING-mediated signaling and ISG expression in patient PBMCs. This work links defective AMFR-STING signaling to severe VZV disease and hyperinflammation and suggests a direct role for cGAS-STING in the control of viral infections in humans. In conclusion, we describe a novel genetic etiology of severe VZV disease in childhood, also representing the first inborn error of immunity related to a defect in the cGAS-STING pathway.
MeSH term(s)	Child, Preschool ; Humans ; Chickenpox ; Herpes Zoster ; Herpesvirus 3, Human/genetics ; Immunity, Innate ; Interferon Type I ; Leukocytes, Mononuclear/metabolism ; Lymphohistiocytosis, Hemophagocytic/diagnosis ; Lymphohistiocytosis, Hemophagocytic/genetics ; Nucleotidyltransferases/genetics ; Nucleotidyltransferases/metabolism ; Pneumonia ; Receptors, Autocrine Motility Factor ; Ubiquitin-Protein Ligases/genetics ; Male
Chemical Substances	AMFR protein, human (EC 2.3.2.27) ; Interferon Type I ; Nucleotidyltransferases (EC 2.7.7.-) ; Receptors, Autocrine Motility Factor (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2024-01-26
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	779361-3
ISSN	1573-2592 ; 0271-9142
ISSN (online)	1573-2592
ISSN	0271-9142
DOI	10.1007/s10875-024-01653-5
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Article ; Online: The presence of interferon affects the progression of non-alcoholic fatty liver disease.

Møhlenberg, Michelle / Eriksen, Peter Lykke / Laursen, Tea Lund / Nielsen, Mette Bak / Hamilton Dutoit, Stephen Jacques / Grønbæk, Henning / Hartmann, Rune / Thomsen, Karen Louise

Genes and immunity

2022 Volume 23, Issue 5, Page(s) 157–165

Abstract: Inflammation and metabolic dysfunction are hallmarks of the progression of non-alcoholic fatty liver disease (NAFLD), which is the fastest-growing liver disease worldwide. Emerging evidence indicates that innate immune mechanisms are essential drivers of ...

Abstract	Inflammation and metabolic dysfunction are hallmarks of the progression of non-alcoholic fatty liver disease (NAFLD), which is the fastest-growing liver disease worldwide. Emerging evidence indicates that innate immune mechanisms are essential drivers of fibrosis development in chronic inflammatory liver diseases, including NAFLD. In this study, 142 NAFLD patients were genotyped for three IFNL4 single-nucleotide variants in order to investigate the genetic relationship between IFNL4 and fibrosis in NAFLD patients. We observed an overrepresentation of the non-functional IFNL4 allele in patients with significant fibrosis (>F2). Next, we investigated the potential protective role of interferon (IFN) in relation to the development of liver fibrosis in an animal model of non-alcoholic steatohepatitis (NASH). In contradiction to our hypothesis, the results showed an increase in fibrosis in IFN treated animals. Our study clearly indicates that IFN is able to affect the development of liver fibrosis, although our clinical and experimental data are conflicting.
MeSH term(s)	Animals ; Antiviral Agents ; Disease Progression ; Fibrosis ; Interferons/genetics ; Liver/metabolism ; Liver/pathology ; Liver Cirrhosis/genetics ; Liver Cirrhosis/metabolism ; Liver Cirrhosis/pathology ; Non-alcoholic Fatty Liver Disease/genetics
Chemical Substances	Antiviral Agents ; Interferons (9008-11-1)
Language	English
Publishing date	2022-06-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2060566-3
ISSN	1476-5470 ; 1466-4879
ISSN (online)	1476-5470
ISSN	1466-4879
DOI	10.1038/s41435-022-00176-6
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Article ; Online: Sensitivity to Vaccines, Therapeutic Antibodies, and Viral Entry Inhibitors and Advances To Counter the SARS-CoV-2 Omicron Variant.

Zhou, Hao / Møhlenberg, Michelle / Thakor, Jigarji C / Tuli, Hardeep Singh / Wang, Pengfei / Assaraf, Yehuda G / Dhama, Kuldeep / Jiang, Shibo

Clinical microbiology reviews

2022 Volume 35, Issue 3, Page(s) e0001422

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps evolving and mutating into newer variants over time, which gain higher transmissibility, disease severity, and spread in communities at a faster rate, resulting in multiple waves of surge ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps evolving and mutating into newer variants over time, which gain higher transmissibility, disease severity, and spread in communities at a faster rate, resulting in multiple waves of surge in Coronavirus Disease 2019 (COVID-19) cases. A highly mutated and transmissible SARS-CoV-2 Omicron variant has recently emerged, driving the extremely high peak of infections in almost all continents at an unprecedented speed and scale. The Omicron variant evades the protection rendered by vaccine-induced antibodies and natural infection, as well as overpowers the antibody-based immunotherapies, raising the concerns of current effectiveness of available vaccines and monoclonal antibody-based therapies. This review outlines the most recent advancements in studying the virology and biology of the Omicron variant, highlighting its increased resistance to current antibody-based therapeutics and its immune escape against vaccines. However, the Omicron variant is highly sensitive to viral fusion inhibitors targeting the HR1 motif in the spike protein, enzyme inhibitors, involving the endosomal fusion pathway, and ACE2-based entry inhibitors. Omicron variant-associated infectivity and entry mechanisms of Omicron variant are essentially distinct from previous characterized variants. Innate sensing and immune evasion of SARS-CoV-2 and T cell immunity to the virus provide new perspectives of vaccine and drug development. These findings are important for understanding SARS-CoV-2 viral biology and advances in developing vaccines, antibody-based therapies, and more effective strategies to mitigate the transmission of the Omicron variant or the next SARS-CoV-2 variant of concern.
MeSH term(s)	Angiotensin-Converting Enzyme 2/antagonists & inhibitors ; Antibodies, Monoclonal/therapeutic use ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/prevention & control ; COVID-19/therapy ; COVID-19/virology ; COVID-19 Vaccines/therapeutic use ; Humans ; SARS-CoV-2/drug effects ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus ; Virus Internalization/drug effects
Chemical Substances	Antibodies, Monoclonal ; Antiviral Agents ; COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2022-06-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645015-5
ISSN	1098-6618 ; 0893-8512
ISSN (online)	1098-6618
ISSN	0893-8512
DOI	10.1128/cmr.00014-22
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Article ; Online: The Impact of IFNλ4 on the Adaptive Immune Response to SARS-CoV-2 Infection.

Møhlenberg, Michelle / Monrad, Ida / Vibholm, Line K / Nielsen, Stine S F / Frattari, Giacomo Schmidt / Schleimann, Mariane Høgsbjerg / Olesen, Rikke / Kjolby, Mads / Gunst, Jesper Damsgaard / Søgaard, Ole Schmeltz / O'Brien, Thomas R / Tolstrup, Martin / Hartmann, Rune

Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

2021 Volume 41, Issue 11, Page(s) 407–414

Abstract: Genetic polymorphisms at ... ...

Abstract	Genetic polymorphisms at the
MeSH term(s)	Adaptive Immunity/genetics ; Adaptive Immunity/immunology ; Adult ; Aged ; CD8-Positive T-Lymphocytes/immunology ; COVID-19/immunology ; Cohort Studies ; Cross-Sectional Studies ; Female ; Genotype ; Humans ; Interleukins/genetics ; Interleukins/immunology ; Male ; Middle Aged ; Polymorphism, Single Nucleotide/genetics ; Polymorphism, Single Nucleotide/immunology ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Young Adult
Chemical Substances	IFNL4 protein, human ; Interleukins
Language	English
Publishing date	2021-11-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	1226675-9
ISSN	1557-7465 ; 1079-9907
ISSN (online)	1557-7465
ISSN	1079-9907
DOI	10.1089/jir.2021.0106
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Article ; Online: The

Zhou, Hao / Møhlenberg, Michelle / Terczyńska-Dyla, Ewa / Winther, Kasper Grønbjerg / Hansen, Nanna Hougaard / Vad-Nielsen, Johan / Laloli, Laura / Dijkman, Ronald / Nielsen, Anders Lade / Gad, Hans Henrik / Hartmann, Rune

Journal of virology

2020 Volume 94, Issue 5

Abstract: Interferon lambda 4 (IFN-λ4) is a recently identified enigmatic member of the interferon (IFN) lambda family. Genetic data suggest that ... ...

Abstract	Interferon lambda 4 (IFN-λ4) is a recently identified enigmatic member of the interferon (IFN) lambda family. Genetic data suggest that the
MeSH term(s)	A549 Cells ; Animals ; Antiviral Agents/pharmacology ; Base Sequence ; Evolution, Molecular ; Gene Expression Regulation ; HEK293 Cells ; Hep G2 Cells ; Hepacivirus/physiology ; Hepatitis C/metabolism ; Humans ; Inflammation ; Interferons/classification ; Interferons/genetics ; Interferons/metabolism ; Interleukins/classification ; Interleukins/genetics ; Interleukins/pharmacology ; Liver/pathology ; RNA, Messenger/metabolism ; Sequence Alignment ; THP-1 Cells
Chemical Substances	Antiviral Agents ; IFNL4 protein, human ; Interleukins ; RNA, Messenger ; Interferons (9008-11-1)
Language	English
Publishing date	2020-02-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01535-19
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