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
AuthorsVenturini, 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
AbstractBackground 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.
KeywordsInfectious Diseases; Immunology and Allergy
Year2024
JournalThe Journal of Infectious Diseases
Journal citationp. jiae001
PublisherOxford University Press (OUP)
ISSN0022-1899
1537-6613
Digital Object Identifier (DOI)https://doi.org/10.1093/infdis/jiae001
Funder/ClientWellcome Trust
National Institute for Health Research
Biomedical Research Centre
Publication dates
Print05 Jan 2024
Online05 Jan 2024
Publication process dates
Accepted03 Jan 2024
Deposited10 Jan 2024
Accepted author manuscript
File Access Level
Open
Licensehttps://creativecommons.org/licenses/by/4.0/
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Manuscript_JID-76895R2.docx
File access level: Open

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