Detection of antiviral drug resistance in patients with congenital cytomegalovirus infection using long-read sequencing: a retrospective observational study
Abstract Background Congenital human cytomegalovirus (cCMV) infection can cause sensorineural hearing loss and neurodevelopmental disabilities in children. Ganciclovir and valganciclovir (GCV/VGCV) improve long-term audiologic and neurodevelopmental outcomes for patients with cCMV infection; however...
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | BMC Infectious Diseases |
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| Online Access: | https://doi.org/10.1186/s12879-022-07537-6 |
| _version_ | 1818250216731574272 |
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| author | Yuka Torii Kazuhiro Horiba Jun-ichi Kawada Kazunori Haruta Makoto Yamaguchi Takako Suzuki Hideko Uryu Naoyuki Kashiwa Keiji Goishi Tomoo Ogi Yoshinori Ito |
| author_facet | Yuka Torii Kazuhiro Horiba Jun-ichi Kawada Kazunori Haruta Makoto Yamaguchi Takako Suzuki Hideko Uryu Naoyuki Kashiwa Keiji Goishi Tomoo Ogi Yoshinori Ito |
| author_sort | Yuka Torii |
| collection | DOAJ |
| description | Abstract Background Congenital human cytomegalovirus (cCMV) infection can cause sensorineural hearing loss and neurodevelopmental disabilities in children. Ganciclovir and valganciclovir (GCV/VGCV) improve long-term audiologic and neurodevelopmental outcomes for patients with cCMV infection; however, antiviral drug resistance has been documented in some cases. Long-read sequencing can be used for the detection of drug resistance mutations. The objective of this study was to develop full-length analysis of UL97 and UL54, target genes with mutations that confer GCV/VGCV resistance using long-read sequencing, and investigate drug resistance mutation in patients with cCMV infection. Methods Drug resistance mutation analysis was retrospectively performed in 11 patients with cCMV infection treated with GCV/VGCV. UL97 and UL54 genes were amplified using blood DNA. The amplicons were sequenced using a long-read sequencer and aligned with the reference gene. Single nucleotide variants were detected and replaced with the reference sequence. The replaced sequence was submitted to a mutation resistance analyzer, which is an open platform for drug resistance mutations. Results Two drug resistance mutations (UL54 V823A and UL97 A594V) were found in one patient. Both mutations emerged after 6 months of therapy, where viral load increased. Mutation rates subsided after cessation of GCV/VGCV treatment. Conclusions Antiviral drug resistance can emerge in patients with cCMV receiving long-term therapy. Full-length analysis of UL97 and UL54 via long-read sequencing enabled the rapid and comprehensive detection of drug resistance mutations. |
| first_indexed | 2024-12-12T15:48:52Z |
| format | Article |
| id | doaj.art-a44d9824281c463286eb6798ca0b7d65 |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-12T15:48:52Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-a44d9824281c463286eb6798ca0b7d652022-12-22T00:19:41ZengBMCBMC Infectious Diseases1471-23342022-06-012211910.1186/s12879-022-07537-6Detection of antiviral drug resistance in patients with congenital cytomegalovirus infection using long-read sequencing: a retrospective observational studyYuka Torii0Kazuhiro Horiba1Jun-ichi Kawada2Kazunori Haruta3Makoto Yamaguchi4Takako Suzuki5Hideko Uryu6Naoyuki Kashiwa7Keiji Goishi8Tomoo Ogi9Yoshinori Ito10Department of Pediatrics, Nagoya University Graduate School of MedicineDepartment of Pediatrics, Nagoya University Graduate School of MedicineDepartment of Pediatrics, Nagoya University Graduate School of MedicineDepartment of Pediatrics, Nagoya University Graduate School of MedicineDepartment of Pediatrics, Nagoya University Graduate School of MedicineDepartment of Pediatrics, Nagoya University Graduate School of MedicineDepartment of Pediatrics, National Center for Global Health and MedicineDepartment of Pediatrics, National Center for Global Health and MedicineDepartment of Pediatrics, National Center for Global Health and MedicineDepartment of Genetics, Research Institute of Environmental Medicine Nagoya UniversityDepartment of Pediatrics, Nagoya University Graduate School of MedicineAbstract Background Congenital human cytomegalovirus (cCMV) infection can cause sensorineural hearing loss and neurodevelopmental disabilities in children. Ganciclovir and valganciclovir (GCV/VGCV) improve long-term audiologic and neurodevelopmental outcomes for patients with cCMV infection; however, antiviral drug resistance has been documented in some cases. Long-read sequencing can be used for the detection of drug resistance mutations. The objective of this study was to develop full-length analysis of UL97 and UL54, target genes with mutations that confer GCV/VGCV resistance using long-read sequencing, and investigate drug resistance mutation in patients with cCMV infection. Methods Drug resistance mutation analysis was retrospectively performed in 11 patients with cCMV infection treated with GCV/VGCV. UL97 and UL54 genes were amplified using blood DNA. The amplicons were sequenced using a long-read sequencer and aligned with the reference gene. Single nucleotide variants were detected and replaced with the reference sequence. The replaced sequence was submitted to a mutation resistance analyzer, which is an open platform for drug resistance mutations. Results Two drug resistance mutations (UL54 V823A and UL97 A594V) were found in one patient. Both mutations emerged after 6 months of therapy, where viral load increased. Mutation rates subsided after cessation of GCV/VGCV treatment. Conclusions Antiviral drug resistance can emerge in patients with cCMV receiving long-term therapy. Full-length analysis of UL97 and UL54 via long-read sequencing enabled the rapid and comprehensive detection of drug resistance mutations.https://doi.org/10.1186/s12879-022-07537-6CytomegalovirusGanciclovirValganciclovirCongenital cytomegalovirus infectionDrug resistanceLong-read sequencing |
| spellingShingle | Yuka Torii Kazuhiro Horiba Jun-ichi Kawada Kazunori Haruta Makoto Yamaguchi Takako Suzuki Hideko Uryu Naoyuki Kashiwa Keiji Goishi Tomoo Ogi Yoshinori Ito Detection of antiviral drug resistance in patients with congenital cytomegalovirus infection using long-read sequencing: a retrospective observational study BMC Infectious Diseases Cytomegalovirus Ganciclovir Valganciclovir Congenital cytomegalovirus infection Drug resistance Long-read sequencing |
| title | Detection of antiviral drug resistance in patients with congenital cytomegalovirus infection using long-read sequencing: a retrospective observational study |
| title_full | Detection of antiviral drug resistance in patients with congenital cytomegalovirus infection using long-read sequencing: a retrospective observational study |
| title_fullStr | Detection of antiviral drug resistance in patients with congenital cytomegalovirus infection using long-read sequencing: a retrospective observational study |
| title_full_unstemmed | Detection of antiviral drug resistance in patients with congenital cytomegalovirus infection using long-read sequencing: a retrospective observational study |
| title_short | Detection of antiviral drug resistance in patients with congenital cytomegalovirus infection using long-read sequencing: a retrospective observational study |
| title_sort | detection of antiviral drug resistance in patients with congenital cytomegalovirus infection using long read sequencing a retrospective observational study |
| topic | Cytomegalovirus Ganciclovir Valganciclovir Congenital cytomegalovirus infection Drug resistance Long-read sequencing |
| url | https://doi.org/10.1186/s12879-022-07537-6 |
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