No evidence for human monocyte-derived macrophage infection and antibody-mediated enhancement of SARS-CoV-2 infection

Vaccines are essential to control the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and to protect the vulnerable population. However, one safety concern of vaccination is the possible development of antibody-dependent enhancement (ADE) of SARS-CoV-2 infection. The potential infection of Fc receptor bearing cells such as macrophages, would support continued virus replication and inflammatory responses, and thereby potentially worsen the clinical outcome of COVID-19. Here we demonstrate that SARS-CoV-2 and SARS-CoV neither infect human monocyte-derived macrophages (hMDM) nor induce inflammatory cytokines in these cells, in sharp contrast to Middle East respiratory syndrome (MERS) coronavirus and the common cold human coronavirus 229E. Furthermore, serum from convalescent COVID-19 patients neither induced enhancement of SARS-CoV-2 infection nor innate immune response in hMDM. Although, hMDM expressed angiotensin-converting enzyme 2, no or very low levels of transmembrane protease serine 2 were found. These results support the view that ADE may not be involved in the immunopathological processes associated with COVID-19, however, more studies are necessary to understand the potential contribution of antibodies-virus complexes with other cells expressing FcR receptors.

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The ADP-ribose-1″-monophosphatase domains of severe acute respiratory syndrome coronavirus and human coronavirus 229E mediate resistance to antiviral interferon responses

Journal of General Virology ◽

10.1099/vir.0.031856-0 ◽

2011 ◽

Vol 92 (8) ◽

pp. 1899-1905 ◽

Cited By ~ 56

Author(s):

Thomas Kuri ◽

Klara K. Eriksson ◽

Akos Putics ◽

Roland Züst ◽

Eric J. Snijder ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Antiviral Effect ◽

Genetically Engineered ◽

Innate Immune ◽

Viral Escape ◽

Innate Immune Responses ◽

Human Coronavirus ◽

Increased Sensitivity ◽

Interferon Responses ◽

Human Coronavirus 229E

Several plus-strand RNA viruses encode proteins containing macrodomains. These domains possess ADP-ribose-1″-phosphatase (ADRP) activity and/or bind poly(ADP-ribose), poly(A) or poly(G). The relevance of these activities in the viral life cycle has not yet been resolved. Here, we report that genetically engineered mutants of severe acute respiratory syndrome coronavirus (SARS-CoV) and human coronavirus 229E (HCoV-229E) expressing ADRP-deficient macrodomains displayed an increased sensitivity to the antiviral effect of alpha interferon compared with their wild-type counterparts. The data suggest that macrodomain-associated ADRP activities may have a role in viral escape from the innate immune responses of the host.

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Pharmacological Activation of p53 during Human Monocyte to Macrophage Differentiation Attenuates Their Pro-Inflammatory Activation by TLR4, TLR7 and TLR8 Agonists

Cancers ◽

10.3390/cancers13050958 ◽

2021 ◽

Vol 13 (5) ◽

pp. 958

Author(s):

Dmitry Namgaladze ◽

Bernhard Brüne

Keyword(s):

Inflammatory Responses ◽

Macrophage Polarization ◽

Human Monocyte ◽

Interleukin 4 ◽

Macrophage Differentiation ◽

Human Macrophages ◽

Transcriptional Signature ◽

Mdm2 Antagonist ◽

P53 Activation ◽

The Impact

The transcription factor p53 has well-recognized roles in regulating cell cycle, DNA damage repair, cell death, and metabolism. It is an important tumor suppressor and pharmacological activation of p53 by interrupting its interaction with the ubiquitin E3 ligase mouse double minute 2 homolog (MDM2) is actively explored for anti-tumor therapies. In immune cells, p53 modulates inflammatory responses, but the impact of p53 on macrophages remains incompletely understood. In this study, we used the MDM2 antagonist idasanutlin (RG7388) to investigate the responses of primary human macrophages to pharmacological p53 activation. Idasanutlin induced a robust p53-dependent transcriptional signature in macrophages, including several pro-apoptotic genes. However, idasanutlin did not generally sensitize macrophages to apoptosis, except for an enhanced response to a Fas-stimulating antibody. In fully differentiated macrophages, idasanutlin did not affect pro-inflammatory gene expression induced by toll-like receptor 4 (TLR4), TLR3, and TLR7/8 agonists, but inhibited interleukin-4-induced macrophage polarization. However, when present during monocyte to macrophage differentiation, idasanutlin attenuated inflammatory responses towards activation of TLR4 and TLR7/8 by low doses of lipopolysaccharide or resiquimod (R848). This was accompanied by a reduced expression of CD14, TLR7, and TLR8 in macrophages differentiated in the presence of idasanutlin. Our data suggest anti-inflammatory effects of pharmacological p53 activation in differentiating human macrophages.

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BRIEF FACTS ABOUT COVID-19 (SARS-CoV-2) and DETAILS

10.31219/osf.io/4mfwa ◽

2021 ◽

Author(s):

Sorush Niknamian

Keyword(s):

Respiratory Tract ◽

Common Cold ◽

Respiratory Tract Infections ◽

Human Coronavirus ◽

The Family ◽

The Common ◽

Human Coronaviruses ◽

The 1960S ◽

Tract Infections ◽

Human Coronavirus 229E

Coronaviruses are a group of related viruses that cause diseases in mammals and birds. In humans, coronaviruses cause respiratory tract infections that can range from mild to lethal. Mild illnesses include some cases of the common cold, while more lethal varieties can cause SARS, MERS, and COVID-19. The outbreak was identified in Wuhan, China, in December 2019, declared to be a Public Health Emergency of International Concern on 30 January 2020, and recognized as a pandemic on 11 March 2020. Coronaviruses are the subfamily Orthocoronavirinae, within the family of Coronaviridae, order Nidovirales, and realm Riboviria. They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses is approximately from 26 to 32 kilobases. Coronaviruses were first discovered in the 1930s and Human coronaviruses were discovered in the 1960s. The earliest ones studied were from human patients with the common cold, which were later named human coronavirus 229E and human coronavirus OC43. Other human coronaviruses have since been identified, including SARS-CoV in 2003, HCoV NL63 in 2004, HKU1 in 2005, MERS-CoV in 2012, and SARS-CoV-2 in 2019. Most of these have involved serious respiratory tract infections

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Brief Facts about COVID-19 (SARS-CoV-2)

Asian Journal of Complementary and Alternative Medicine ◽

10.53043/2347-3894.acam90001 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Sorush Niknamian

Keyword(s):

Respiratory Tract ◽

Common Cold ◽

Respiratory Tract Infections ◽

Human Coronavirus ◽

The Family ◽

The Common ◽

Human Coronaviruses ◽

The 1960S ◽

Tract Infections ◽

Human Coronavirus 229E

Coronaviruses are a group of related viruses that cause diseases in mammals and birds. In humans, coronaviruses cause respiratory tract infections that can range from mild to lethal. Mild illnesses include some cases of the common cold, while more lethal varieties can cause SARS, MERS, and COVID-19. The outbreak was identified in Wuhan, China, in December 2019, declared to be a Public Health Emergency of International Concern on 30 January 2020, and recognized as a pandemic on 11 March 2020. Coronaviruses are the subfamily Orthocoronavirinae, within the family of Coronaviridae, order Nidovirales, and realm Riboviria. They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses is approximately from 26 to 32 kilobases. Coronaviruses were first discovered in the 1930s and Human coronaviruses were discovered in the 1960s. The earliest ones studied were from human patients with the common cold, which were later named human coronavirus 229E and human coronavirus OC43. Other human coronaviruses have since been identified, including SARS-CoV in 2003, HCoV NL63 in 2004, HKU1 in 2005, MERS-CoV in 2012, and SARS-CoV-2 in 2019. Most of these have involved serious respiratory tract infections

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Lessons Learned From Serial Isolations Of Human Coronavirus 229E From Environmental Surfaces Of A Classroom During Influenza Season

10.31988/scitrends.16688 ◽

2018 ◽

Author(s):

John Lednicky

Keyword(s):

Influenza Season ◽

Lessons Learned ◽

Human Coronavirus ◽

Environmental Surfaces ◽

Human Coronavirus 229E

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Deubiquitinase Activity and Regulation of Antiviral Innate Immune Responses by Papain-like Proteases of Human Coronavirus NL63*

PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS ◽

10.3724/sp.j.1206.2010.00111 ◽

2010 ◽

Vol 37 (8) ◽

pp. 871-880 ◽

Cited By ~ 5

Author(s):

Li SUN ◽

Yu-Dong YANG ◽

Dian-Bo LIU ◽

Ya-Ling XING ◽

Xiao-Juan CHEN ◽

...

Keyword(s):

Immune Responses ◽

Innate Immune ◽

Innate Immune Responses ◽

Human Coronavirus

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SARS-CoV-2 spike protein S1 subunit induces pro-inflammatory responses via toll-like receptor 4 signaling in murine and human macrophages

Heliyon ◽

10.1016/j.heliyon.2021.e06187 ◽

2021 ◽

Vol 7 (2) ◽

pp. e06187 ◽

Cited By ~ 2

Author(s):

Ken Shirato ◽

Takako Kizaki

Keyword(s):

Inflammatory Responses ◽

Spike Protein ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Human Macrophages

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A protocol for adding knowledge to Wikidata: aligning resources on human coronaviruses

BMC Biology ◽

10.1186/s12915-020-00940-y ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Andra Waagmeester ◽

Egon L. Willighagen ◽

Andrew I. Su ◽

Martina Kutmon ◽

Jose Emilio Labra Gayo ◽

...

Keyword(s):

Common Ground ◽

Knowledge Bases ◽

Public Knowledge ◽

Medical Problems ◽

Human Coronavirus ◽

Data Schema ◽

Helping Others ◽

Human Coronaviruses ◽

The Right ◽

Human Coronavirus 229E

Abstract Background Pandemics, even more than other medical problems, require swift integration of knowledge. When caused by a new virus, understanding the underlying biology may help finding solutions. In a setting where there are a large number of loosely related projects and initiatives, we need common ground, also known as a “commons.” Wikidata, a public knowledge graph aligned with Wikipedia, is such a commons and uses unique identifiers to link knowledge in other knowledge bases. However, Wikidata may not always have the right schema for the urgent questions. In this paper, we address this problem by showing how a data schema required for the integration can be modeled with entity schemas represented by Shape Expressions. Results As a telling example, we describe the process of aligning resources on the genomes and proteomes of the SARS-CoV-2 virus and related viruses as well as how Shape Expressions can be defined for Wikidata to model the knowledge, helping others studying the SARS-CoV-2 pandemic. How this model can be used to make data between various resources interoperable is demonstrated by integrating data from NCBI (National Center for Biotechnology Information) Taxonomy, NCBI Genes, UniProt, and WikiPathways. Based on that model, a set of automated applications or bots were written for regular updates of these sources in Wikidata and added to a platform for automatically running these updates. Conclusions Although this workflow is developed and applied in the context of the COVID-19 pandemic, to demonstrate its broader applicability it was also applied to other human coronaviruses (MERS, SARS, human coronavirus NL63, human coronavirus 229E, human coronavirus HKU1, human coronavirus OC4).

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Terminal uridyltransferase 7 regulates TLR4-triggered inflammation by controlling Regnase-1 mRNA uridylation and degradation

Nature Communications ◽

10.1038/s41467-021-24177-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Chia-Ching Lin ◽

Yi-Ru Shen ◽

Chi-Chih Chang ◽

Xiang-Yi Guo ◽

Yun-Yun Young ◽

...

Keyword(s):

Posttranscriptional Regulation ◽

Inflammatory Responses ◽

Rna Stability ◽

Innate Immune ◽

Stem Loop ◽

Stem Loop Structure ◽

Tlr4 Activation ◽

Harmful Effects ◽

Different Levels

AbstractDifferent levels of regulatory mechanisms, including posttranscriptional regulation, are needed to elaborately regulate inflammatory responses to prevent harmful effects. Terminal uridyltransferase 7 (TUT7) controls RNA stability by adding uridines to its 3′ ends, but its function in innate immune response remains obscure. Here we reveal that TLR4 activation induces TUT7, which in turn selectively regulates the production of a subset of cytokines, including Interleukin 6 (IL-6). TUT7 regulates IL-6 expression by controlling ribonuclease Regnase-1 mRNA (encoded by Zc3h12a gene) stability. Mechanistically, TLR4 activation causes TUT7 to bind directly to the stem-loop structure on Zc3h12a 3′-UTR, thereby promotes Zc3h12a uridylation and degradation. Zc3h12a from LPS-treated TUT7-sufficient macrophages possesses increased oligo-uridylated ends with shorter poly(A) tails, whereas oligo-uridylated Zc3h12a is significantly reduced in Tut7-/- cells after TLR4 activation. Together, our findings reveal the functional role of TUT7 in sculpting TLR4-driven responses by modulating mRNA stability of a selected set of inflammatory mediators.

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