Human Cytomegalovirus Genomes Sequenced Directly From Clinical Material: Variation, Multiple-Strain Infection, Recombination, and Gene Loss

Nicolás M. Suárez, Gavin S. Wilkie, Elias Hage, Salvatore Camiolo, Marylouisa Holton, Joseph Hughes, Maha Maabar, Sreenu B. Vattipally, Akshay Dhingra, Ursula A. Gompels, Gavin W.G. Wilkinson, Fausto Baldanti, Milena Furione, Daniele Lilleri, Alessia Arossa, Tina Ganzenmueller, Giuseppe Gerna, Petr Hubáček, Thomas F. Schulz, Dana WolfMaurizio Zavattoni, Andrew J. Davison

Research output: Contribution to journalArticle

Abstract

The genomic characteristics of human cytomegalovirus (HCMV) strains sequenced directly from clinical pathology samples were investigated, focusing on variation, multiple-strain infection, recombination, and gene loss. A total of 207 datasets generated in this and previous studies using target enrichment and high-throughput sequencing were analyzed, in the process enabling the determination of genome sequences for 91 strains. Key findings were that (i) it is important to monitor the quality of sequencing libraries in investigating variation; (ii) many recombinant strains have been transmitted during HCMV evolution, and some have apparently survived for thousands of years without further recombination; (iii) mutants with nonfunctional genes (pseudogenes) have been circulating and recombining for long periods and can cause congenital infection and resulting clinical sequelae; and (iv) intrahost variation in single-strain infections is much less than that in multiple-strain infections. Future population-based studies are likely to continue illuminating the evolution, epidemiology, and pathogenesis of HCMV.

Original languageEnglish
Pages (from-to)781-791
Number of pages11
JournalThe Journal of infectious diseases
Volume220
Issue number5
DOIs
Publication statusPublished - Jul 31 2019

Keywords

  • gene loss
  • genome sequence
  • genotype
  • human cytomegalovirus
  • multiple-strain infection
  • mutation
  • recombination
  • target enrichment
  • variation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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  • Cite this

    Suárez, N. M., Wilkie, G. S., Hage, E., Camiolo, S., Holton, M., Hughes, J., Maabar, M., Vattipally, S. B., Dhingra, A., Gompels, U. A., Wilkinson, G. W. G., Baldanti, F., Furione, M., Lilleri, D., Arossa, A., Ganzenmueller, T., Gerna, G., Hubáček, P., Schulz, T. F., ... Davison, A. J. (2019). Human Cytomegalovirus Genomes Sequenced Directly From Clinical Material: Variation, Multiple-Strain Infection, Recombination, and Gene Loss. The Journal of infectious diseases, 220(5), 781-791. https://doi.org/10.1093/infdis/jiz208