Christian Berg1,2,3, Mette M Rosenkilde4, Thomas Benfield5, Lene Nielsen6, Thomas Sundelin6, Hans R Lüttichau7,8. 1. Infectious Diseases Unit, Department of Medicine, Copenhagen University Hospital, Herlev Gentofte, DK-2730, Herlev, Denmark. Christian.Berg@regionh.dk. 2. Center for Research and Disruption of Infectious Diseases (CREDID), Department of Infectious Diseases, Copenhagen University Hospital, Amager Hvidovre, DK-2650, Hvidovre, Denmark. Christian.Berg@regionh.dk. 3. Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark. Christian.Berg@regionh.dk. 4. Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark. 5. Center for Research and Disruption of Infectious Diseases (CREDID), Department of Infectious Diseases, Copenhagen University Hospital, Amager Hvidovre, DK-2650, Hvidovre, Denmark. 6. Department of Clinical Microbiology, Copenhagen University Hospital, Herlev Gentofte, DK-2730, Herlev, Denmark. 7. Infectious Diseases Unit, Department of Medicine, Copenhagen University Hospital, Herlev Gentofte, DK-2730, Herlev, Denmark. Hans.Rudolf.von.Luttichau@regionh.dk. 8. Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark. Hans.Rudolf.von.Luttichau@regionh.dk.
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.
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.
Authors: Steven Sijmons; Kim Thys; Mirabeau Mbong Ngwese; Ellen Van Damme; Jan Dvorak; Marnix Van Loock; Guangdi Li; Ruth Tachezy; Laurent Busson; Jeroen Aerssens; Marc Van Ranst; Piet Maes Journal: J Virol Date: 2015-05-13 Impact factor: 5.103
Authors: Daniel E Noyola; Beatriz H Valdez-López; Alba E Hernández-Salinas; Miguel A Santos-Díaz; Miguel A Noyola-Frías; Juan F Reyes-Macías; Leticia G Martínez-Martínez Journal: Arch Med Res Date: 2005 Sep-Oct Impact factor: 2.235
Authors: J Grosjean; L Trapes; S Hantz; C Mengelle; B Virey; F Undreiner; V Messager; F Denis; B Marin; S Alain Journal: J Clin Virol Date: 2014-08-17 Impact factor: 3.168
Authors: M E Penfold; D J Dairaghi; G M Duke; N Saederup; E S Mocarski; G W Kemble; T J Schall Journal: Proc Natl Acad Sci U S A Date: 1999-08-17 Impact factor: 11.205
Authors: Nicolás M Suárez; Gavin S Wilkie; Elias Hage; Salvatore Camiolo; Marylouisa Holton; Joseph Hughes; Maha Maabar; Sreenu B Vattipally; Akshay Dhingra; Ursula A Gompels; Gavin W G Wilkinson; Fausto Baldanti; Milena Furione; Daniele Lilleri; Alessia Arossa; Tina Ganzenmueller; Giuseppe Gerna; Petr Hubáček; Thomas F Schulz; Dana Wolf; Maurizio Zavattoni; Andrew J Davison Journal: J Infect Dis Date: 2019-07-31 Impact factor: 5.226
Authors: Christian Berg; Michael J Wedemeyer; Motiejus Melynis; Roman R Schlimgen; Lasse H Hansen; Jon Våbenø; Francis C Peterson; Brian F Volkman; Mette M Rosenkilde; Hans R Lüttichau Journal: PLoS Pathog Date: 2022-03-10 Impact factor: 6.823