Novel Viral Sequences in a Patient with Cryptogenic Liver Cirrhosis Revealed by Serum Virome Sequencing
Clinical studies indicate the etiology of liver disease to be unknown in 5% to 30% of patients. A long-standing hypothesis is the existence of unknown viruses beyond hepatitis A through E virus. We conducted serum virome sequencing in nine patients with cryptogenic liver disease and identified eight...
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2025-06-01
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| Online Access: | https://www.mdpi.com/1999-4915/17/6/812 |
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| author | Xiaoan Zhang Ida X. Fan Yanjuan Xu Jody Rule Long Ping Victor Tse Mahmoud Reza Pourkarim William M. Lee Adrian M. Di Bisceglie Xiaofeng Fan |
| author_facet | Xiaoan Zhang Ida X. Fan Yanjuan Xu Jody Rule Long Ping Victor Tse Mahmoud Reza Pourkarim William M. Lee Adrian M. Di Bisceglie Xiaofeng Fan |
| author_sort | Xiaoan Zhang |
| collection | DOAJ |
| description | Clinical studies indicate the etiology of liver disease to be unknown in 5% to 30% of patients. A long-standing hypothesis is the existence of unknown viruses beyond hepatitis A through E virus. We conducted serum virome sequencing in nine patients with cryptogenic liver disease and identified eight contigs that could not be annotated. One was determined to be a contaminant, while two of seven contigs from an individual (Patient 3) were validated by reverse transcription and polymerase chain reaction (RT-PCR) and Sanger sequencing. The possibility of contamination was completely excluded through PCR, with templates extracted using different methods from samples taken at different time points. One of the contigs, Seq260, was characterized as negative-sense single-stranded DNA via enzymatic digestion and genome walking. Digital-droplet PCR revealed the copy number of Seq260 to be low: 343 copies/mL. Seq260-based nested PCR screening was negative in 200 blood donors and 225 patients with liver disease with/without known etiologies. None of the seven contigs from Patient 3 was mapped onto 118,713 viral metagenomic data. Conclusively, we discovered seven unknown contigs from a patient with cryptogenic liver cirrhosis. These sequences are likely from a novel human virus with a negative-sense, linear single-stranded DNA genome. |
| format | Article |
| id | doaj-art-4644f2e369e34bc29a87ae6b27728efb |
| institution | Kabale University |
| issn | 1999-4915 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-4644f2e369e34bc29a87ae6b27728efb2025-08-20T03:32:32ZengMDPI AGViruses1999-49152025-06-0117681210.3390/v17060812Novel Viral Sequences in a Patient with Cryptogenic Liver Cirrhosis Revealed by Serum Virome SequencingXiaoan Zhang0Ida X. Fan1Yanjuan Xu2Jody Rule3Long Ping Victor Tse4Mahmoud Reza Pourkarim5William M. Lee6Adrian M. Di Bisceglie7Xiaofeng Fan8Division of Gastroenterology & Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO 63104, USADepartment of Microbiology & Immunology, Saint Louis University School of Medicine, St. Louis, MO 63104, USADivision of Gastroenterology & Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO 63104, USADivision of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Microbiology & Immunology, Saint Louis University School of Medicine, St. Louis, MO 63104, USALaboratory for Clinical and Epidemiological Virology, Rega Institute, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, BelgiumDivision of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADivision of Gastroenterology & Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO 63104, USADivision of Gastroenterology & Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO 63104, USAClinical studies indicate the etiology of liver disease to be unknown in 5% to 30% of patients. A long-standing hypothesis is the existence of unknown viruses beyond hepatitis A through E virus. We conducted serum virome sequencing in nine patients with cryptogenic liver disease and identified eight contigs that could not be annotated. One was determined to be a contaminant, while two of seven contigs from an individual (Patient 3) were validated by reverse transcription and polymerase chain reaction (RT-PCR) and Sanger sequencing. The possibility of contamination was completely excluded through PCR, with templates extracted using different methods from samples taken at different time points. One of the contigs, Seq260, was characterized as negative-sense single-stranded DNA via enzymatic digestion and genome walking. Digital-droplet PCR revealed the copy number of Seq260 to be low: 343 copies/mL. Seq260-based nested PCR screening was negative in 200 blood donors and 225 patients with liver disease with/without known etiologies. None of the seven contigs from Patient 3 was mapped onto 118,713 viral metagenomic data. Conclusively, we discovered seven unknown contigs from a patient with cryptogenic liver cirrhosis. These sequences are likely from a novel human virus with a negative-sense, linear single-stranded DNA genome.https://www.mdpi.com/1999-4915/17/6/812etiologyhepatitis viruscryptogenic liver diseasecryptogenic cirrhosisvirome |
| spellingShingle | Xiaoan Zhang Ida X. Fan Yanjuan Xu Jody Rule Long Ping Victor Tse Mahmoud Reza Pourkarim William M. Lee Adrian M. Di Bisceglie Xiaofeng Fan Novel Viral Sequences in a Patient with Cryptogenic Liver Cirrhosis Revealed by Serum Virome Sequencing Viruses etiology hepatitis virus cryptogenic liver disease cryptogenic cirrhosis virome |
| title | Novel Viral Sequences in a Patient with Cryptogenic Liver Cirrhosis Revealed by Serum Virome Sequencing |
| title_full | Novel Viral Sequences in a Patient with Cryptogenic Liver Cirrhosis Revealed by Serum Virome Sequencing |
| title_fullStr | Novel Viral Sequences in a Patient with Cryptogenic Liver Cirrhosis Revealed by Serum Virome Sequencing |
| title_full_unstemmed | Novel Viral Sequences in a Patient with Cryptogenic Liver Cirrhosis Revealed by Serum Virome Sequencing |
| title_short | Novel Viral Sequences in a Patient with Cryptogenic Liver Cirrhosis Revealed by Serum Virome Sequencing |
| title_sort | novel viral sequences in a patient with cryptogenic liver cirrhosis revealed by serum virome sequencing |
| topic | etiology hepatitis virus cryptogenic liver disease cryptogenic cirrhosis virome |
| url | https://www.mdpi.com/1999-4915/17/6/812 |
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