Allelic and haplotypic diversity of 5′promoter region of the MICA gene

Luo, Jia; Tian, Wei; Pan, Fenghua; Liu, XueXiang; Li, Lixin

doi:10.1016/j.humimm.2013.12.010

Cited by 7 publications

(26 citation statements)

References 23 publications

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“…Moreover, the IE2-consensus sequence we identified is conserved among different allelic variants of MICA promoter (C. Fionda and C. Cerboni, unpublished observations, and Ref. 72,73), suggesting that during the virus/host coevolution, a positive selection of promoter sequences in MICA alleles carrying the IE2 DNA binding site occurred, with the host likely making IE2 useful for its own cellular gene expression as well. The second question is how can we reconcile the observed HMCV-triggered increase of activating ligands with the immunoevasion strategies evolved by the virus to target the same molecules?…”

Section: Discussionmentioning

confidence: 83%

Distinct Roles for Human Cytomegalovirus Immediate Early Proteins IE1 and IE2 in the Transcriptional Regulation of MICA and PVR/CD155 Expression

Pignoloni

Fionda

Dell’Oste

et al. 2016

The Journal of Immunology

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Elimination of virus-infected cells by cytotoxic lymphocytes is triggered by activating receptors, among which NKG2D and DNAM-1/CD226 play an important role. Their ligands, that is, MHC class I–related chain (MIC) A/B and UL16-binding proteins (ULBP)1–6 (NKG2D ligand), Nectin-2/CD112, and poliovirus receptor (PVR)/CD155 (DNAM-1 ligand), are often induced on virus-infected cells, although some viruses, including human CMV (HCMV), can block their expression. In this study, we report that infection of different cell types with laboratory or low-passage HCMV strains upregulated MICA, ULBP3, and PVR, with NKG2D and DNAM-1 playing a role in NK cell–mediated lysis of infected cells. Inhibition of viral DNA replication with phosphonoformic acid did not prevent ligand upregulation, thus indicating that early phases of HCMV infection are involved in ligand increase. Indeed, the major immediate early (IE) proteins IE1 and IE2 stimulated the expression of MICA and PVR, but not ULBP3. IE2 directly activated MICA promoter via its binding to an IE2-responsive element that we identified within the promoter and that is conserved among different alleles of MICA. Both IE proteins were instead required for PVR upregulation via a mechanism independent of IE DNA binding activity. Finally, inhibiting IE protein expression during HCMV infection confirmed their involvement in ligand increase. We also investigated the contribution of the DNA damage response, a pathway activated by HCMV and implicated in ligand regulation. However, silencing of ataxia telangiectasia mutated, ataxia telangiectasia and Rad3–related protein, and DNA-dependent protein kinase did not influence ligand expression. Overall, these data reveal that MICA and PVR are directly regulated by HCMV IE proteins, and this may be crucial for the onset of an early host antiviral response.

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Section: Discussionmentioning

confidence: 83%

Distinct Roles for Human Cytomegalovirus Immediate Early Proteins IE1 and IE2 in the Transcriptional Regulation of MICA and PVR/CD155 Expression

Pignoloni

Fionda

Dell’Oste

et al. 2016

The Journal of Immunology

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“…The ethnicity of sample CB71 was African Caribbean, and MICA exons 2-6 typing by SBT revealed MICA*004. Previously, MICA*004 was found to be exclusively associated with MICA-P7 promoter (Cox et al, 2014;Luo et al, 2014), and it is therefore likely that MICA-P13 has arisen by point mutation with putative implications for expression of this MICA*004 allele.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies reveal that the promoter region sequence is more ancient than the coding region, as multiple alleles are associated with one promoter, such as MICA-P7 (Cox et al, 2014;Luo et al, 2014), indicating that extracellular polymorphism and diversity occurred later. Fourteen different promoter variants are now known for the MICA gene, with potential for differential expression levels.…”

Section: Discussionmentioning

confidence: 99%

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Two novel 5′ promoter sequences of the MHC class I‐related chain A gene

Laza-Briviesca

Madrigal

Cox

2015

Int J Immunogenetics

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“…A MICA promoter fragment of 647 bp and MICB fragment of 581 bp was amplified by polymerase chain reaction (PCR) and sequenced in both directions for analysis of positions −560 to −1. This polymorphic region in the 5'UTR of both genes was shown to contain most regulatory elements involved in promoter transcriptional activity as discussed in our previous report and studies published by Luo et al and Pan et al…”

Section: Methodsmentioning

confidence: 99%

Diversity and characterisation of polymorphic 3' untranslated region haplotypes of MICA and MICB genes

Cox

Hernandez

Danby

et al. 2018

HLA

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MICA and MICB genes encode ligands that interact with the natural killer (NK) cell activating receptor, NKG2D. These ligands display a highly polymorphic allelic repertoire, although the true functional significance of this polymorphism remains elusive. We previously reported additional polymorphism in the 5' untranslated region (UTR) proximal promoter region of these genes by sequencing international histocompatibility workshop (IHW) cell line DNA promoter and coding regions. The present study extends this analysis by further characterising the 3'UTR region of the same IHW reference panel to achieve a more complete understanding of MICA and MICB haplotype diversity and possible functional relevance. We found 17 extended MICA haplotypes encompassing the coding region and 3'UTR, including four novel haplotypes identified in IHW cell line DNA. This increased to 21 when also considering the 5'UTR proximal promoter region. Analysis of the MICB 3'UTR revealed two novel sequences in cell lines KLO and WIN designated MICB‐UTR8 and UTR9, respectively. A total of 11 MICB haplotypes were identified in this study and five were unique. The present study, characterising MICA/B 3'UTR polymorphism utilising IHW reference cell lines, could be useful for future studies investigating the role of microRNA in post‐transcriptional repression of gene expression and for immunotherapy strategies to combat cancer progression.

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Allelic and haplotypic diversity of 5′promoter region of the MICA gene

Cited by 7 publications

References 23 publications

Distinct Roles for Human Cytomegalovirus Immediate Early Proteins IE1 and IE2 in the Transcriptional Regulation of MICA and PVR/CD155 Expression

Distinct Roles for Human Cytomegalovirus Immediate Early Proteins IE1 and IE2 in the Transcriptional Regulation of MICA and PVR/CD155 Expression

Two novel 5′ promoter sequences of the MHC class I‐related chain A gene

Diversity and characterisation of polymorphic 3' untranslated region haplotypes of MICA and MICB genes

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