Persistent Low-Level Variants in a Subset of Viral Genes Are Highly Predictive of Poor Outcome in Immunocompromised Patients With Cytomegalovirus Infection
Journal article
Venturini, C., Colston, Julia M, Charles, Oscar, Lankina, Anastasia, Best, Timothy, Atkinson, Claire, Forrest, Calum, Williams, Charlotte A, Rao, Kanchan, Worth, Austen, Thorburn, Doug, Harber, Mark, Griffiths, Paul and Breuer, Judith (2024). Persistent Low-Level Variants in a Subset of Viral Genes Are Highly Predictive of Poor Outcome in Immunocompromised Patients With Cytomegalovirus Infection. The Journal of Infectious Diseases. p. jiae001. https://doi.org/10.1093/infdis/jiae001
Authors | Venturini, C., Colston, Julia M, Charles, Oscar, Lankina, Anastasia, Best, Timothy, Atkinson, Claire, Forrest, Calum, Williams, Charlotte A, Rao, Kanchan, Worth, Austen, Thorburn, Doug, Harber, Mark, Griffiths, Paul and Breuer, Judith |
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Abstract | Background Human cytomegalovirus (HCMV) is the most common and serious opportunistic infection after solid organ and hematopoietic stem cell transplantation. In this study, we used whole-genome HCMV data to investigate viral factors associated with the clinical outcome. Methods We sequenced HCMV samples from 16 immunocompromised pediatric patients with persistent viremia. Eight of the 16 patients died of complications due to HCMV infection. We also sequenced samples from 35 infected solid organ adult recipients, of whom 1 died with HCMV infection. Results We showed that samples from both groups have fixed variants at resistance sites and mixed infections. Next-generation sequencing also revealed nonfixed variants at resistance sites in most of the patients who died (6/9). A machine learning approach identified 10 genes with nonfixed variants in these patients. These genes formed a viral signature that discriminated patients with HCMV infection who died from those who survived with high accuracy (area under the curve = 0.96). Lymphocyte numbers for a subset of patients showed no recovery posttransplant in the patients who died. Conclusions We hypothesize that the viral signature identified in this study may be a useful biomarker for poor response to antiviral drug treatment and indirectly for poor T-cell function, potentially identifying early those patients requiring nonpharmacological interventions. |
Keywords | Infectious Diseases; Immunology and Allergy |
Year | 2024 |
Journal | The Journal of Infectious Diseases |
Journal citation | p. jiae001 |
Publisher | Oxford University Press (OUP) |
ISSN | 0022-1899 |
1537-6613 | |
Digital Object Identifier (DOI) | https://doi.org/10.1093/infdis/jiae001 |
Funder/Client | Wellcome Trust |
National Institute for Health Research | |
Biomedical Research Centre | |
Publication dates | |
05 Jan 2024 | |
Online | 05 Jan 2024 |
Publication process dates | |
Accepted | 03 Jan 2024 |
Deposited | 10 Jan 2024 |
Accepted author manuscript | File Access Level Open |
License | https://creativecommons.org/licenses/by/4.0/ |
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