To the Editor Murine gammaherpesvirus 68 (MHV‐68) escapes from NK‐cell‐mediated immune surveillance by a CEACAM1‐mediated immune evasion mechanism

Adler, Heiko; Steer, Beatrix; Juskewitz, Eric; Kammerer, Robert

doi:10.1002/eji.201444593

Cited by 7 publications

(6 citation statements)

References 10 publications

(12 reference statements)

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“…Because KS is a highly angiogenic tumor, we wanted to investigate the induction of CEACAM1 expression by vIL-6. Furthermore, CEACAM1 and a CEACAM1 homolog have been shown to contribute to the pathogenesis of other herpesviruses, but the role of CEACAM1 during KSHV infection has not yet been investigated ( 47 , 66 , 67 ).…”

Section: Discussionmentioning

confidence: 99%

“…Previous microarray studies of immortalized dermal microvascular endothelial cells infected with KSHV also reported that the gene for CEACAM1 was one of multiple genes affected by KSHV infection ( 69 ). Furthermore, CEACAM1 was found to be upregulated in the lungs of mice infected with the murine gammaherpesvirus MHV68 ( 66 , 67 ). In the present study, we found that both KSHV latent and de novo infection of endothelial cells upregulated CEACAM1 expression compared to that in uninfected cells, and reactivation of PEL also resulted in increased CEACAM1 expression.…”

Section: Discussionmentioning

confidence: 99%

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Kaposi's Sarcoma-Associated Herpesvirus Interleukin-6 Modulates Endothelial Cell Movement by Upregulating Cellular Genes Involved in Migration

Giffin

West

Damania

2015

mBio

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Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of human Kaposi’s sarcoma, a tumor that arises from endothelial cells, as well as two B cell lymphoproliferative diseases, primary effusion lymphoma and multicentric Castleman’s disease. KSHV utilizes a variety of mechanisms to evade host immune responses and promote cellular transformation and growth in order to persist for the life of the host. A viral homolog of human interleukin-6 (hIL-6) named viral interleukin-6 (vIL-6) is encoded by KSHV and expressed in KSHV-associated cancers. Similar to hIL-6, vIL-6 is secreted, but the majority of vIL-6 is retained within the endoplasmic reticulum, where it can initiate functional signaling through part of the interleukin-6 receptor complex. We sought to determine how intracellular vIL-6 modulates the host endothelial cell environment by analyzing vIL-6’s impact on the endothelial cell transcriptome. vIL-6 significantly altered the expression of many cellular genes associated with cell migration. In particular, vIL-6 upregulated the host factor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) at the protein and message levels. CEACAM1 has been implicated in tumor invasion and metastasis and promotes migration and vascular remodeling in endothelial cells. We report that vIL-6 upregulates CEACAM1 by a STAT3-dependent mechanism and that CEACAM1 promotes vIL-6-mediated migration. Furthermore, latent and de novo KSHV infections of endothelial cells also induce CEACAM1 expression. Collectively, our data suggest that vIL-6 modulates endothelial cell migration by upregulating the expression of cellular factors, including CEACAM1.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Kaposi's Sarcoma-Associated Herpesvirus Interleukin-6 Modulates Endothelial Cell Movement by Upregulating Cellular Genes Involved in Migration

Giffin

West

Damania

2015

mBio

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“…The murine gammaherpesvirus MHV-68 upregulates the inhibitory receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) on alveolar epithelial cells, and there are indications that this upregulation, via homophilic trans interactions with CEACAM1 on NK cells, may result in suppressed NK cell activity (122).…”

Section: Herpesvirus Nk Cell Evasion Strategiesmentioning

confidence: 99%

Herpesvirus Evasion of Natural Killer Cells

Pelsmaeker

Romero

Vitale

et al. 2018

J Virol

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Natural killer (NK) cells play an important role in the host response against viral infections and cancer development. They are able to kill virus-infected and tumor cells, and they produce different important cytokines that stimulate the antiviral and antitumor adaptive immune response, particularly interferon gamma. NK cells are of particular importance in herpesvirus infections, which is illustrated by systemic and life-threatening herpesvirus disease symptoms in patients with deficiencies in NK cell activity and by the myriad of reports describing herpesvirus NK cell evasion strategies. The latter is particularly obvious for cytomegaloviruses, but increasing evidence indicates that most, if not all, members of the herpesvirus family suppress NK cell activity to some extent. This review discusses the different NK cell evasion strategies described for herpesviruses and how this knowledge may translate to clinical applications.

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“…Among those are SIRPα and CEACAM1 and CEACAM3, members of the human carcinoembryonic antigen-related cell-cell adhesion molecule (CEACAM) family which have inhibitory ITIM/ ITSM motifs and activating ITAM-like motifs in their cytoplasmic regions, respectively [3,4]. A number of bacterial pathogens like pathogenic Neisseria (N. gonorrhoeae, N. meningitis) Haemophilus influenzae and Moraxella catarrhalis have been shown to bind to the N-terminal immunoglobulin (Ig) variable-like domain of CEACAM1 on epithelial and immune cells allowing both entry into the host by transcytosis and downregulation of the host's immune response by inhibiting adaptive and innate immune reactions [5][6][7][8][9][10][11]. Pathogens thus exploit the normal physiological function of CEA-CAM1 which acts as an immune inhibitory receptor on leukocytes upon homotypic or heterotypic interactions for example with other CEACAM members [7,12].…”

Section: Introductionmentioning

confidence: 99%

Coevolution of paired receptors in Xenopus carcinoembryonic antigen-related cell adhesion molecule families suggests appropriation as pathogen receptors

Zimmermann

Kammerer

2016

BMC Genomics

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BackgroundIn mammals, CEACAM1 and closely related members represent paired receptors with similar extracellular ligand-binding regions and cytoplasmic domains with opposing functions. Human CEACAM1 and CEACAM3 which have inhibitory ITIM/ITSM and activating ITAM-like motifs, respectively, in their cytoplasmic regions are such paired receptors. Various bacterial pathogens bind to CEACAM1 on epithelial and immune cells facilitating both entry into the host and down-regulation of the immune response whereas interaction with granulocyte-specific CEACAM3 leads to their uptake and destruction. It is unclear whether paired CEACAM receptors also exist in other vertebrate clades.ResultsWe identified more than 80 ceacam genes in Xenopus tropicalis and X. laevis. They consist of two subgroups containing one or two putative paired receptor pairs each. Analysis of genomic sequences of paired receptors provide evidence that their highly similar ligand binding domains were adjusted by recent gene conversion events. In contrast, selection for diversification is observed among inhibitory receptor orthologs of the two frogs which split some 60 million years ago. The allotetraploid X. laevis arose later by hybridization of two closely related species. Interestingly, despite the conservation of the genomic landscape surrounding the homeologous ceacam loci only one locus resembles the one found in X. tropicalis. From the second X. laevis locus more than 80 % of the ceacam genes were lost including 5 of the 6 paired receptor genes. This suggests that once the gene for one of the paired receptors is lost the remaining gene cluster degrades rapidly probably due to lack of selection pressure exerted by pathogens.ConclusionsThe presence of paired receptors and selection for diversification suggests that also in amphibians CEACAM1-related inhibitory proteins are or were used as pathogen receptors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3279-9) contains supplementary material, which is available to authorized users.

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To the Editor Murine gammaherpesvirus 68 (MHV‐68) escapes from NK‐cell‐mediated immune surveillance by a CEACAM1‐mediated immune evasion mechanism

Cited by 7 publications

References 10 publications

Kaposi's Sarcoma-Associated Herpesvirus Interleukin-6 Modulates Endothelial Cell Movement by Upregulating Cellular Genes Involved in Migration

Kaposi's Sarcoma-Associated Herpesvirus Interleukin-6 Modulates Endothelial Cell Movement by Upregulating Cellular Genes Involved in Migration

Herpesvirus Evasion of Natural Killer Cells

Coevolution of paired receptors in Xenopus carcinoembryonic antigen-related cell adhesion molecule families suggests appropriation as pathogen receptors

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