Viral Manipulation of Host Inhibitory Receptor Signaling for Immune Evasion

Ong, Eugenia Z.; Chan, Kap Luk; Ooi, Eng Eong

doi:10.1371/journal.ppat.1005776

Cited by 19 publications

(25 citation statements)

References 49 publications

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“…To counter this early activating FcγR-triggered antiviral response, DENV co-ligates the inhibitory leukocyte immunoglobulin-like receptor B1 (LILRB1) during ADE6. LILRB1 recruits SH2 domain-containing phosphatase-1 (SHP-1) to dephosphorylate Syk and downregulate STAT-1 induction of ISG response67.…”

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confidence: 99%

Dengue virus compartmentalization during antibody-enhanced infection

Ong

Zhang

Tan

et al. 2017

Sci Rep

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Secondary infection with a heterologous dengue virus (DENV) serotype increases the risk of severe dengue, through a process termed antibody-dependent enhancement (ADE). During ADE, DENV is opsonized with non- or sub-neutralizing antibody levels that augment entry into monocytes and dendritic cells through Fc-gamma receptors (FcγRs). We previously reported that co-ligation of leukocyte immunoglobulin-like receptor-B1 (LILRB1) by antibody-opsonized DENV led to recruitment of SH2 domain-containing phosphatase-1 (SHP-1) to dephosphorylate spleen tyrosine kinase (Syk) and reduce interferon stimulated gene induction. Here, we show that LILRB1 also signals through SHP-1 to attenuate the otherwise rapid acidification for lysosomal enzyme activation following FcγR-mediated uptake of DENV. Reduced or slower trafficking of antibody-opsonized DENV to lytic phagolysosomal compartments, demonstrates how co-ligation of LILRB1 also permits DENV to overcome a cell-autonomous immune response, enhancing intracellular survival of DENV. Our findings provide insights on how antiviral drugs that modify phagosome acidification should be used for viruses such as DENV.

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confidence: 99%

Dengue virus compartmentalization during antibody-enhanced infection

Ong

Zhang

Tan

et al. 2017

Sci Rep

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“…16 The viral mediated manipulations of the host immune-cell receptor signaling is well established fact; however, any such evidence specific to SARS-CoV-2 is currently scarce in literature. 17 In absence of significant cell-surface expression of ACE2 in immune system components, the alternative mechanisms which are exploited by the COVID-19 virus to induce immunopathology, need to be ascertained. Therefore, our finding warrants for a systematic review of existing literature indicated for the set of plausible mechanisms which may explain immunological dysregulation in COVID-19 without the involvement of ACE2 signaling.…”

Section: Resultsmentioning

confidence: 99%

Expression of SARS-CoV-2 host cell entry factors in immune system components of healthy individuals and its relevance for COVID-19 immunopathology

Kumar

Narayan

Kumar

et al. 2020

Preprint

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Introduction: Intense immunological dysregulation including immune cell lesions have been characteristically observed in severe cases of Coronavirus Disease-2019 (COVID-19), for which molecular mechanisms are least understood. A study of physiological expressions of SARS-CoV-2 host cell entry related factors in immune system components may help explain molecular mechanisms involved in COVID-19 immunopathology. Materials and Methods: Transcriptomic and proteomic expression metadata for SARS-CoV-2 host cell entry receptor ACE2 and entry associated proteases (TMPRSS2, CTSL, and FURIN) were analysed in silico across immune system components including blood lineage cells. Results: ACE2 was not-detected in any of the studied immune cell components, however, varying transcriptomic and proteomic expressions were observed, for TMPRSS2, CTSL, and FURIN. Conclusions: Non-detectable expressions of SARS-CoV-2 host cell entry receptor ACE2 in immune system components or blood lineage cells indicate it doesn't mediate immune cell lesions in COVID-19. Alternative mechanisms need to be explored for COVID-19 immuno-pathogenesis.

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“…On the other hand, it has also been reported that the presence of long stalks in Ig superfamily members could allow a better exposure of the Ig domains in the plasma membrane, favoring interactions with their ligands [58,59]. This might be of special relevance if these molecules work by modulating the activity of particular immune cells by engaging inhibitory receptors [60].…”

Section: Discussionmentioning

confidence: 99%

Divergent Traits and Ligand-Binding Properties of the Cytomegalovirus CD48 Gene Family

Martínez-Vicente

Farré²,

Engel³

et al. 2020

Viruses

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The genesis of gene families by the capture of host genes and their subsequent duplication is a crucial process in the evolution of large DNA viruses. CD48 is a cell surface molecule that interacts via its N-terminal immunoglobulin (Ig) domain with the cell surface receptor 2B4 (CD244), regulating leukocyte cytotoxicity. We previously reported the presence of five CD48 homologs (vCD48s) in two related cytomegaloviruses, and demonstrated that one of them, A43, binds 2B4 and acts as a soluble CD48 decoy receptor impairing NK cell function. Here, we have characterized the rest of these vCD48s. We show that they are highly glycosylated proteins that display remarkably distinct features: divergent biochemical properties, cellular locations, and temporal expression kinetics. In contrast to A43, none of them interacts with 2B4. Consistent with this, molecular modeling of the N-terminal Ig domains of these vCD48s evidences notable changes as compared to CD48, suggesting that they interact with alternative targets. Accordingly, we demonstrate that one of them, S30, tightly binds CD2, a crucial T- and NK-cell adhesion and costimulatory molecule. Thus, our findings show how a key host immune receptor gene captured by a virus can be subsequently remodeled to evolve new immunoevasins with altered binding properties.

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Viral Manipulation of Host Inhibitory Receptor Signaling for Immune Evasion

Cited by 19 publications

References 49 publications

Dengue virus compartmentalization during antibody-enhanced infection

Dengue virus compartmentalization during antibody-enhanced infection

Expression of SARS-CoV-2 host cell entry factors in immune system components of healthy individuals and its relevance for COVID-19 immunopathology

Divergent Traits and Ligand-Binding Properties of the Cytomegalovirus CD48 Gene Family

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