The frequency of cytomegalovirus non-ELR UL146 genotypes in neonates with congenital CMV disease is comparable to strains in the background population
Abstract Background Congenital cytomegalovirus disease (cCMV) is common and can be fatal or cause severe sequelae. Circulating strains of cytomegalovirus carry a high number of variable or disrupted genes. One of these is UL146, a highly diverse gene with 14 distinct genotypes encoding a CXC-chemoki...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-04-01
|
| Series: | BMC Infectious Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12879-021-06076-w |
| _version_ | 1818561797859311616 |
|---|---|
| author | Christian Berg Mette M. Rosenkilde Thomas Benfield Lene Nielsen Thomas Sundelin Hans R. Lüttichau |
| author_facet | Christian Berg Mette M. Rosenkilde Thomas Benfield Lene Nielsen Thomas Sundelin Hans R. Lüttichau |
| author_sort | Christian Berg |
| collection | DOAJ |
| description | Abstract Background Congenital cytomegalovirus disease (cCMV) is common and can be fatal or cause severe sequelae. Circulating strains of cytomegalovirus carry a high number of variable or disrupted genes. One of these is UL146, a highly diverse gene with 14 distinct genotypes encoding a CXC-chemokine involved in viral dissemination. UL146 genotypes 5 and 6 lack the conserved ELR motif, potentially affecting strain virulence. Here, we investigate whether UL146 genotypes 5 and 6 were associated with congenital CMV infection. Methods Viral DNA was extracted and UL146 sequenced from 116 neonatal dried blood spots (DBS) stored in the Danish National Biobank since 1982 and linked to registered cCMV cases through a personal identifier. These sequences were compared to UL146 control sequences obtained from CMV DNA extracted from 83 urine samples from children with suspected bacterial urinary tract infections. Results Three non-ELR UL146 genotypes (5 and 6) were observed among the cases (2.6%) and two were observed among the controls (2.4%; P > 0.99). Additionally, no significant association with cCMV was found for the other 12 genotypes in a post-hoc analysis, although genotype 8 showed a tendency to be more frequent among cases with 12 observations against three (P = 0.10). All fourteen genotypes were found to have little intra-genotype variation. Viral load, gender, and sample age were not found to be associated with any particular UL146 genotype. Conclusions No particular UL146 genotype was associated with cCMV in this nationwide retrospective case-control study. Associations between CMV disease and disrupted or polymorph CMV genes among immunosuppressed people living with HIV/AIDS and transplant recipients should be investigated in future studies. |
| first_indexed | 2024-12-14T00:55:25Z |
| format | Article |
| id | doaj.art-79e0eca8c3624963b1544bc69fb5da08 |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-14T00:55:25Z |
| publishDate | 2021-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-79e0eca8c3624963b1544bc69fb5da082022-12-21T23:23:36ZengBMCBMC Infectious Diseases1471-23342021-04-0121111210.1186/s12879-021-06076-wThe frequency of cytomegalovirus non-ELR UL146 genotypes in neonates with congenital CMV disease is comparable to strains in the background populationChristian Berg0Mette M. Rosenkilde1Thomas Benfield2Lene Nielsen3Thomas Sundelin4Hans R. Lüttichau5Infectious Diseases Unit, Department of Medicine, Copenhagen University HospitalLaboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of CopenhagenCenter for Research and Disruption of Infectious Diseases (CREDID), Department of Infectious Diseases, Copenhagen University HospitalDepartment of Clinical Microbiology, Copenhagen University HospitalDepartment of Clinical Microbiology, Copenhagen University HospitalInfectious Diseases Unit, Department of Medicine, Copenhagen University HospitalAbstract Background Congenital cytomegalovirus disease (cCMV) is common and can be fatal or cause severe sequelae. Circulating strains of cytomegalovirus carry a high number of variable or disrupted genes. One of these is UL146, a highly diverse gene with 14 distinct genotypes encoding a CXC-chemokine involved in viral dissemination. UL146 genotypes 5 and 6 lack the conserved ELR motif, potentially affecting strain virulence. Here, we investigate whether UL146 genotypes 5 and 6 were associated with congenital CMV infection. Methods Viral DNA was extracted and UL146 sequenced from 116 neonatal dried blood spots (DBS) stored in the Danish National Biobank since 1982 and linked to registered cCMV cases through a personal identifier. These sequences were compared to UL146 control sequences obtained from CMV DNA extracted from 83 urine samples from children with suspected bacterial urinary tract infections. Results Three non-ELR UL146 genotypes (5 and 6) were observed among the cases (2.6%) and two were observed among the controls (2.4%; P > 0.99). Additionally, no significant association with cCMV was found for the other 12 genotypes in a post-hoc analysis, although genotype 8 showed a tendency to be more frequent among cases with 12 observations against three (P = 0.10). All fourteen genotypes were found to have little intra-genotype variation. Viral load, gender, and sample age were not found to be associated with any particular UL146 genotype. Conclusions No particular UL146 genotype was associated with cCMV in this nationwide retrospective case-control study. Associations between CMV disease and disrupted or polymorph CMV genes among immunosuppressed people living with HIV/AIDS and transplant recipients should be investigated in future studies.https://doi.org/10.1186/s12879-021-06076-wUL146vCXCL1ELRDBScCMVCytomegalovirus |
| spellingShingle | Christian Berg Mette M. Rosenkilde Thomas Benfield Lene Nielsen Thomas Sundelin Hans R. Lüttichau The frequency of cytomegalovirus non-ELR UL146 genotypes in neonates with congenital CMV disease is comparable to strains in the background population BMC Infectious Diseases UL146 vCXCL1 ELR DBS cCMV Cytomegalovirus |
| title | The frequency of cytomegalovirus non-ELR UL146 genotypes in neonates with congenital CMV disease is comparable to strains in the background population |
| title_full | The frequency of cytomegalovirus non-ELR UL146 genotypes in neonates with congenital CMV disease is comparable to strains in the background population |
| title_fullStr | The frequency of cytomegalovirus non-ELR UL146 genotypes in neonates with congenital CMV disease is comparable to strains in the background population |
| title_full_unstemmed | The frequency of cytomegalovirus non-ELR UL146 genotypes in neonates with congenital CMV disease is comparable to strains in the background population |
| title_short | The frequency of cytomegalovirus non-ELR UL146 genotypes in neonates with congenital CMV disease is comparable to strains in the background population |
| title_sort | frequency of cytomegalovirus non elr ul146 genotypes in neonates with congenital cmv disease is comparable to strains in the background population |
| topic | UL146 vCXCL1 ELR DBS cCMV Cytomegalovirus |
| url | https://doi.org/10.1186/s12879-021-06076-w |
| work_keys_str_mv | AT christianberg thefrequencyofcytomegalovirusnonelrul146genotypesinneonateswithcongenitalcmvdiseaseiscomparabletostrainsinthebackgroundpopulation AT mettemrosenkilde thefrequencyofcytomegalovirusnonelrul146genotypesinneonateswithcongenitalcmvdiseaseiscomparabletostrainsinthebackgroundpopulation AT thomasbenfield thefrequencyofcytomegalovirusnonelrul146genotypesinneonateswithcongenitalcmvdiseaseiscomparabletostrainsinthebackgroundpopulation AT lenenielsen thefrequencyofcytomegalovirusnonelrul146genotypesinneonateswithcongenitalcmvdiseaseiscomparabletostrainsinthebackgroundpopulation AT thomassundelin thefrequencyofcytomegalovirusnonelrul146genotypesinneonateswithcongenitalcmvdiseaseiscomparabletostrainsinthebackgroundpopulation AT hansrluttichau thefrequencyofcytomegalovirusnonelrul146genotypesinneonateswithcongenitalcmvdiseaseiscomparabletostrainsinthebackgroundpopulation AT christianberg frequencyofcytomegalovirusnonelrul146genotypesinneonateswithcongenitalcmvdiseaseiscomparabletostrainsinthebackgroundpopulation AT mettemrosenkilde frequencyofcytomegalovirusnonelrul146genotypesinneonateswithcongenitalcmvdiseaseiscomparabletostrainsinthebackgroundpopulation AT thomasbenfield frequencyofcytomegalovirusnonelrul146genotypesinneonateswithcongenitalcmvdiseaseiscomparabletostrainsinthebackgroundpopulation AT lenenielsen frequencyofcytomegalovirusnonelrul146genotypesinneonateswithcongenitalcmvdiseaseiscomparabletostrainsinthebackgroundpopulation AT thomassundelin frequencyofcytomegalovirusnonelrul146genotypesinneonateswithcongenitalcmvdiseaseiscomparabletostrainsinthebackgroundpopulation AT hansrluttichau frequencyofcytomegalovirusnonelrul146genotypesinneonateswithcongenitalcmvdiseaseiscomparabletostrainsinthebackgroundpopulation |