Human cytomegalovirus haplotype reconstruction reveals high diversity due to superinfection and evidence of within-host recombination
Abstract
Human cytomegalovirus (HCMV) is a major global cause of congenital disability and transplant-related morbidity. Excessive levels of within-host HCMV nucleotide diversity are attributed to unexpectedly high mutation rates. Here, we show that high HCMV diversity is due to the frequent presence of mixed infections with genetically distinct strains, whereas HCMV in nonmixed infections is no more diverse than other DNA viruses. Using serial patient samples, we reconstruct viral strain haplotypes to pinpoint the timing of HCMV superinfections occurring within the study sampling time frame and uncover within-host viral recombination. From these results, we identify likely sources of infection and demonstrate probable selection for recombinant viruses. These results generate new, yet testable, insights into putative viral and host drivers of HCMV evolution and pathogenesis.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- March 2019
- DOI:
- 10.1073/pnas.1818130116
- Bibcode:
- 2019PNAS..116.5693C