HLA-E restricted cytomegalovirus UL40 peptide polymorphism may represent a risk factor following congenital infection
Abstract Background Congenital cytomegalovirus immunopathogenesis is largely unknown and multifactorial due to the complex interactions between viral, maternal, placental, and child factors. Polymorphisms in the HLA-E binding UL4015-23 peptide mimics HLA-E complexed peptides from certain HLA-A, -B,...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-06-01
|
| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12864-022-08689-0 |
| _version_ | 1818249835981045760 |
|---|---|
| author | David Tarragó Irene González Maria Francisca González-Escribano |
| author_facet | David Tarragó Irene González Maria Francisca González-Escribano |
| author_sort | David Tarragó |
| collection | DOAJ |
| description | Abstract Background Congenital cytomegalovirus immunopathogenesis is largely unknown and multifactorial due to the complex interactions between viral, maternal, placental, and child factors. Polymorphisms in the HLA-E binding UL4015-23 peptide mimics HLA-E complexed peptides from certain HLA-A, -B, -C and -G alleles, which regulate the cellular immune response driven by natural killer-cells (NK) and CD8 + T cells. The aim of this study was to compare UL4015-23 peptides distribution in congenital CMV and the counterpart HLA Class I peptides in a healthy cohort to investigate risk factors and markers for cCMV disease. In this 10-year retrospective study, the UL40 gene was directly sequenced from 242 clinical samples from 199 cases of congenital CMV (166 children and 33 pregnant or breast feeding women). Distribution of HLA-E binding UL4015-23 peptides was analyzed and compared to those of HLA Class I observed in a cohort of 444 healthy individuals. Results Nineteen different HLA-E binding UL4015-23 peptides were found. Three of them (VMAPRTLIL, VMAPRTLLL, VMAPRTLVL) were found in 88.3% of UL40 and 100% of HLA Class I of healthy individuals. In contrast, 15 of them (10.7%) were not found in HLA Class I. The VMAPRTLFL peptide was found in 1% of UL40 and all HLA-G alleles. Significant differences in peptide (VMAPRTLIL, VMAPRTLLL, VMAPRTLVL, other UL4015-23 peptides, other HLA Class I peptides) distribution between UL4015-23 from congenital CMV and HLA-A, -B, -C and –G from healthy individuals were found. Conclusions Our findings suggest that a mismatch between UL4015-23 peptides and HLA Class I peptides between children and mothers might play a role in congenital CMV disease, and it may account for differences in outcome, morbidity and sequelae. |
| first_indexed | 2024-12-12T15:42:49Z |
| format | Article |
| id | doaj.art-715f313a7a984b48954151838561f678 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-12T15:42:49Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-715f313a7a984b48954151838561f6782022-12-22T00:19:52ZengBMCBMC Genomics1471-21642022-06-012311710.1186/s12864-022-08689-0HLA-E restricted cytomegalovirus UL40 peptide polymorphism may represent a risk factor following congenital infectionDavid Tarragó0Irene González1Maria Francisca González-Escribano2National Center for Microbiology, Instituto de Salud Carlos IIINational Center for Microbiology, Instituto de Salud Carlos IIIDepartment of Immunology, Virgen del Rocío Universitary Hospital (IBiS, CSIC, US)Abstract Background Congenital cytomegalovirus immunopathogenesis is largely unknown and multifactorial due to the complex interactions between viral, maternal, placental, and child factors. Polymorphisms in the HLA-E binding UL4015-23 peptide mimics HLA-E complexed peptides from certain HLA-A, -B, -C and -G alleles, which regulate the cellular immune response driven by natural killer-cells (NK) and CD8 + T cells. The aim of this study was to compare UL4015-23 peptides distribution in congenital CMV and the counterpart HLA Class I peptides in a healthy cohort to investigate risk factors and markers for cCMV disease. In this 10-year retrospective study, the UL40 gene was directly sequenced from 242 clinical samples from 199 cases of congenital CMV (166 children and 33 pregnant or breast feeding women). Distribution of HLA-E binding UL4015-23 peptides was analyzed and compared to those of HLA Class I observed in a cohort of 444 healthy individuals. Results Nineteen different HLA-E binding UL4015-23 peptides were found. Three of them (VMAPRTLIL, VMAPRTLLL, VMAPRTLVL) were found in 88.3% of UL40 and 100% of HLA Class I of healthy individuals. In contrast, 15 of them (10.7%) were not found in HLA Class I. The VMAPRTLFL peptide was found in 1% of UL40 and all HLA-G alleles. Significant differences in peptide (VMAPRTLIL, VMAPRTLLL, VMAPRTLVL, other UL4015-23 peptides, other HLA Class I peptides) distribution between UL4015-23 from congenital CMV and HLA-A, -B, -C and –G from healthy individuals were found. Conclusions Our findings suggest that a mismatch between UL4015-23 peptides and HLA Class I peptides between children and mothers might play a role in congenital CMV disease, and it may account for differences in outcome, morbidity and sequelae.https://doi.org/10.1186/s12864-022-08689-0Congenital CMVUL40 peptideImmunomodulatory geneUL40 variabilityHLA-E |
| spellingShingle | David Tarragó Irene González Maria Francisca González-Escribano HLA-E restricted cytomegalovirus UL40 peptide polymorphism may represent a risk factor following congenital infection BMC Genomics Congenital CMV UL40 peptide Immunomodulatory gene UL40 variability HLA-E |
| title | HLA-E restricted cytomegalovirus UL40 peptide polymorphism may represent a risk factor following congenital infection |
| title_full | HLA-E restricted cytomegalovirus UL40 peptide polymorphism may represent a risk factor following congenital infection |
| title_fullStr | HLA-E restricted cytomegalovirus UL40 peptide polymorphism may represent a risk factor following congenital infection |
| title_full_unstemmed | HLA-E restricted cytomegalovirus UL40 peptide polymorphism may represent a risk factor following congenital infection |
| title_short | HLA-E restricted cytomegalovirus UL40 peptide polymorphism may represent a risk factor following congenital infection |
| title_sort | hla e restricted cytomegalovirus ul40 peptide polymorphism may represent a risk factor following congenital infection |
| topic | Congenital CMV UL40 peptide Immunomodulatory gene UL40 variability HLA-E |
| url | https://doi.org/10.1186/s12864-022-08689-0 |
| work_keys_str_mv | AT davidtarrago hlaerestrictedcytomegalovirusul40peptidepolymorphismmayrepresentariskfactorfollowingcongenitalinfection AT irenegonzalez hlaerestrictedcytomegalovirusul40peptidepolymorphismmayrepresentariskfactorfollowingcongenitalinfection AT mariafranciscagonzalezescribano hlaerestrictedcytomegalovirusul40peptidepolymorphismmayrepresentariskfactorfollowingcongenitalinfection |