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

The genomic characteristics of human cytomegalovirus (HCMV) strains sequenced directly from clinical material were investigated, focusing on variation, multiple-strain infection, recombination and natural mutation. A total of 207 datasets generated in this and other studies using target enrichment and high-throughput sequencing were analysed, in the process facilitating the determination of genome sequences for 91 strains. Key findings were that (i) it is vital to monitor sequence data quality, especially when analysing intrahost diversity, (ii) intrahost diversity in single-strain infections is much less than that in multiple-strain infections, (iii) many recombinant strains have been generated and transmitted during HCMV evolution, and some have survived for thousands of years without further recombination, (iv) mutants lacking gene functions have been circulating and recombining for long periods and can cause congenital infection and resulting clinical sequelae. Future studies in general populations are likely to continue illuminating the evolution, epidemiology and pathogenesis of HCMV.