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J Infect Dis. 2019 May 2. pii: jiz208. doi: 10.1093/infdis/jiz208. [Epub ahead of print]

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

Author information

1
MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
2
Institute of Virology, Hannover Medical School, Hannover, Germany.
3
German Center for Infection Research, Hannover-Braunschweig Site, Germany.
4
Pathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.
5
Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
6
Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
7
Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
8
Laboratory of Genetics-Transplantology and Cardiovascular Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
9
Departments of Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
10
Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Tuebingen, Germany.
11
Department of Medical Microbiology, Motol University Hospital, Prague, Czech Republic.
12
Clinical Virology Unit, Department of Clinical Microbiology and Infectious Diseases, Hadassah University Hospital, Jerusalem, Israel.

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 analysed, 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 non-functional 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.

KEYWORDS:

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

PMID:
31050742
DOI:
10.1093/infdis/jiz208

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