Whole-Genome Approach to Assessing Human Cytomegalovirus Dynamics in Transplant Patients Undergoing Antiviral Therapy

Frontiers in Cellular and Infection Microbiology

Thomas F. Schulz¹  Rory Gunson²  Barry Slobedman³  David Gottlieb⁴  Wilfried Gwinner⁵  Albert Heim⁸  Tina Ganzenmueller⁸  Akshay Dhingra⁸  Nicolás M. Suárez⁹  Salvatore Camiolo⁹  Andrew J. Davison⁹  Kathy Li⁹  Silvia Linnenweber-Held^1,10  Emily Blyth^1,11  Barbara Withers^1,12  Selmir Avdic^1,12 

[1] 0German Center for Infection Research, Hanover, Germany;1West of Scotland Specialist Virology Centre, Glasgow Royal Infirmary, Glasgow, United Kingdom;2Discipline of Infectious Diseases and Immunology, Faculty of Medicine and Health, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia;Blood and Bone Marrow Transplant Unit, Westmead Hospital, Sydney, NSW, Australia;Department of Nephrology, Hannover Medical School, Hanover, Germany;Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia;Institute for Medical Virology, University Hospital Tübingen, Tübingen, Germany;Institute of Virology, Hannover Medical School, Hanover, Germany;MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom;Public Health Agency of Lower Saxony, Hanover, Germany;Sydney Cellular Therapies Laboratory, Westmead Hospital, Sydney, NSW, Australia;Westmead Institute for Medical Research, Sydney, NSW, Australia;

关键词: human cytomegalovirus;    transplantation;    genome sequence;    target enrichment;    multiple-strain infection;    antiviral therapy;   

DOI  :  10.3389/fcimb.2020.00267

来源: DOAJ

【 摘 要 】

Human cytomegalovirus (HCMV) is the most frequent cause of opportunistic viral infection following transplantation. Viral factors of potential clinical importance include the selection of mutants resistant to antiviral drugs and the occurrence of infections involving multiple HCMV strains. These factors are typically addressed by analyzing relevant HCMV genes by PCR and Sanger sequencing, which involves independent assays of limited sensitivity. To assess the dynamics of viral populations with high sensitivity, we applied high-throughput sequencing coupled with HCMV-adapted target enrichment to samples collected longitudinally from 11 transplant recipients (solid organ, n = 9, and allogeneic hematopoietic stem cell, n = 2). Only the latter presented multiple-strain infections. Four cases presented resistance mutations (n = 6), two (A594V and L595S) at high (100%) and four (V715M, V781I, A809V, and T838A) at low (<25%) frequency. One allogeneic hematopoietic stem cell transplant recipient presented up to four resistance mutations, each at low frequency. The use of high-throughput sequencing to monitor mutations and strain composition in people at risk of HCMV disease is of potential value in helping clinicians implement the most appropriate therapy.

【 授权许可】

Unknown