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Human cytomegalovirus haplotype reconstruction reveals high diversity due to superinfection and evidence of within-host recombination.

Abstract：

:Recent sequencing efforts have led to estimates of human cytomegalovirus (HCMV) genome-wide intrahost diversity that rival those of persistent RNA viruses [Renzette N, Bhattacharjee B, Jensen JD, Gibson L, Kowalik TF (2011) PLoS Pathog 7:e1001344]. Here, we deep sequence HCMV genomes recovered from single and longitudinally collected blood samples from immunocompromised children to show that the observations of high within-host HCMV nucleotide diversity are explained by the frequent occurrence of mixed infections caused by genetically distant strains. To confirm this finding, we reconstructed within-host viral haplotypes from short-read sequence data. We verify that within-host HCMV nucleotide diversity in unmixed infections is no greater than that of other DNA viruses analyzed by the same sequencing and bioinformatic methods and considerably less than that of human immunodeficiency and hepatitis C viruses. By resolving individual viral haplotypes within patients, we reconstruct the timing, likely origins, and natural history of superinfecting strains. We uncover evidence for within-host recombination between genetically distinct HCMV strains, observing the loss of the parental virus containing the nonrecombinant fragment. The data suggest selection for strains containing the recombinant fragment, generating testable hypotheses about HCMV evolution and pathogenesis. These results highlight that high HCMV diversity present in some samples is caused by coinfection with multiple distinct strains and provide reassurance that within the host diversity for single-strain HCMV infections is no greater than for other herpesviruses.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Cudini J,Roy S,Houldcroft CJ,Bryant JM,Depledge DP,Tutill H,Veys P,Williams R,Worth AJJ,Tamuri AU,Goldstein RA,Breuer J

doi

10.1073/pnas.1818130116

subject

Has Abstract

pub_date

2019-03-19 00:00:00

pages

5693-5698

issue

eissn

0027-8424

issn

1091-6490

pii

1818130116

journal_volume

116

pub_type

杂志文章

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Human cytomegalovirus haplotype reconstruction reveals high diversity due to superinfection and evidence of within-host recombination.