title: Characterising variation in five genetic loci of cytomegalovirus during treatment for congenital infection.
abstract: Cytomegalovirus (CMV) is the most common congenital infection in humans and a leading cause of sensorineural hearing loss. Ganciclovir (6 mg/kg twice daily for 42 days) has been shown to reduce hearing deterioration and is used in clinical practice. Vaccines and passive administration of antibody are being evaluated in randomized controlled trials in allograft candidates, women of childbearing age, and pregnant women with primary CMV infection. To help define genetic variation in each of the targets of these therapeutic interventions, we amplified and sequenced genes UL97 (site utilised for ganciclovir phosphorylation), UL55 (glycoprotein B (gB) vaccine target) and UL128, UL130, and UL131a (specific monoclonal antibody targets). Serial blood, saliva, and urine samples (total 120) obtained from nine infants with symptomatic congenital CMV treated with 42 days' ganciclovir were analyzed. All samples tested were UL97 wild type at baseline and none developed mutations during treatment, showing no selection of resistance. The prevalences of UL55 genotypes were 28% gB1, 22% gB2, 1% gB3, and mixed in 20% samples. No mutations were noted in UL128-131a. Phylogenetic tree analysis showed that sequences with variations were found in multiple body sites of individual patients, so there was no evidence of body site compartmentalization of particular strains of CMV. The significance of these results for changes in diagnostic practices and therapeutic interventions against CMV are discussed. J. Med. Virol. 89:502-507, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Paediatric Infectious Diseases Research Group, St George's University of London, Cranmer Terrace, London, United Kingdom.
authors.forename: Seilesh
authors.initials: S
authors.lastname: Kadambari
authors.affiliation: Centre for Virology, University College London Medical School, Rowland Hill Street, London, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Atkinson
authors.affiliation: Paediatric Infectious Diseases Research Group, St George's University of London, Cranmer Terrace, London, United Kingdom.|Centre for Virology, University College London Medical School, Rowland Hill Street, London, United Kingdom.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Luck
authors.affiliation: Centre for Virology, University College London Medical School, Rowland Hill Street, London, United Kingdom.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Macartney
authors.affiliation: Centre for Virology, University College London Medical School, Rowland Hill Street, London, United Kingdom.
authors.forename: Tim
authors.initials: T
authors.lastname: Conibear
authors.affiliation: Centre for Virology, University College London Medical School, Rowland Hill Street, London, United Kingdom.|European Reference Laboratory Network for Human Influenza, Public Health England, 61 Colindale Avenue, London, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Harrison
authors.affiliation: Centre for Virology, University College London Medical School, Rowland Hill Street, London, United Kingdom.
authors.forename: Clare
authors.initials: C
authors.lastname: Booth
authors.affiliation: Paediatric Infectious Diseases Research Group, St George's University of London, Cranmer Terrace, London, United Kingdom.
authors.forename: Mike
authors.initials: M
authors.lastname: Sharland
authors.affiliation: Centre for Virology, University College London Medical School, Rowland Hill Street, London, United Kingdom.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Griffiths
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D001769:Blood / Q000821:virology; D016000:Cluster Analysis; D003587:Cytomegalovirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000188:drug therapy*; D024882:Drug Resistance, Viral; D015774:Ganciclovir / Q000627:therapeutic use; D056426:Genetic Loci; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D009154:Mutation; D010802:Phylogeny; D012463:Saliva / Q000821:virology; D014556:Urine / Q000821:virology; D014764:Viral Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000998:Antiviral Agents; D014764:Viral Proteins; D015774:Ganciclovir
keywords: antiviral; congenital; cytomegalovirus; resistance; vaccine