Kadambari, S;
Atkinson, C;
Luck, S;
Macartney, M;
Conibear, T;
Harrison, I;
Booth, C;
... Griffiths, PD; + view all
(2017)
Characterising variation in five genetic loci of cytomegalovirus during treatment for congenital infection.
Journal of Medical Virology
, 89
(3)
pp. 502-507.
10.1002/jmv.24654.
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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. © 2016 Wiley Periodicals, Inc.
| Type: | Article |
|---|---|
| Title: | Characterising variation in five genetic loci of cytomegalovirus during treatment for congenital infection |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/jmv.24654 |
| Publisher version: | http://dx.doi.org/10.1002/jmv.24654 |
| Language: | English |
| Additional information: | This is the peer reviewed version of the following article: Kadambari, S., Atkinson, C., Luck, S., Macartney, M., Conibear, T., Harrison, I., Booth, C., Sharland, M. and Griffiths, P. D. (2016), Characterising variation in five genetic loci of cytomegalovirus during treatment for congenital infection. J. Med. Virol., which has been published in final form at http://dx.doi.org/10.1002/jmv.24654. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
| Keywords: | Antiviral, congenital, cytomegalovirus, resistance, vaccine |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1508736 |
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