In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 1 ( 2022-1-4), p. e1010193-
Abstract:
The chimpanzee cytomegalovirus (CCMV) is the closest relative of human CMV (HCMV). Because of the high conservation between these two species and the ability of human cells to fully support CCMV replication, CCMV holds great potential as a model system for HCMV. To make the CCMV genome available for precise and rapid gene manipulation techniques, we captured the genomic DNA of CCMV strain Heberling as a bacterial artificial chromosome (BAC). Selected BAC clones were reconstituted to infectious viruses, growing to similar high titers as parental CCMV. DNA sequencing confirmed the integrity of our clones and led to the identification of two polymorphic loci and a deletion-prone region within the CCMV genome. To re-evaluate the CCMV coding potential, we analyzed the viral transcriptome and proteome and identified several novel ORFs, splice variants, and regulatory RNAs. We further characterized the dynamics of CCMV gene expression and found that viral proteins cluster into five distinct temporal classes. In addition, our datasets revealed that the host response to CCMV infection and the de-regulation of cellular pathways are in line with known hallmarks of HCMV infection. In a first functional experiment, we investigated a proposed frameshift mutation in UL128 that was suspected to restrict CCMV’s cell tropism. In fact, repair of this frameshift re-established productive CCMV infection in endothelial and epithelial cells, expanding the options of CCMV as an infection model. Thus, BAC-cloned CCMV can serve as a powerful tool for systematic approaches in comparative functional genomics, exploiting the close phylogenetic relationship between CCMV and HCMV.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010193
DOI:
10.1371/journal.ppat.1010193.g001
DOI:
10.1371/journal.ppat.1010193.g002
DOI:
10.1371/journal.ppat.1010193.g003
DOI:
10.1371/journal.ppat.1010193.g004
DOI:
10.1371/journal.ppat.1010193.g005
DOI:
10.1371/journal.ppat.1010193.g006
DOI:
10.1371/journal.ppat.1010193.g007
DOI:
10.1371/journal.ppat.1010193.g008
DOI:
10.1371/journal.ppat.1010193.s001
DOI:
10.1371/journal.ppat.1010193.s002
DOI:
10.1371/journal.ppat.1010193.s003
DOI:
10.1371/journal.ppat.1010193.s004
DOI:
10.1371/journal.ppat.1010193.s005
DOI:
10.1371/journal.ppat.1010193.s006
DOI:
10.1371/journal.ppat.1010193.s007
DOI:
10.1371/journal.ppat.1010193.s008
DOI:
10.1371/journal.ppat.1010193.s009
DOI:
10.1371/journal.ppat.1010193.s010
DOI:
10.1371/journal.ppat.1010193.s011
DOI:
10.1371/journal.ppat.1010193.s012
DOI:
10.1371/journal.ppat.1010193.s013
DOI:
10.1371/journal.ppat.1010193.s014
DOI:
10.1371/journal.ppat.1010193.s015
DOI:
10.1371/journal.ppat.1010193.s016
DOI:
10.1371/journal.ppat.1010193.s017
DOI:
10.1371/journal.ppat.1010193.s018
DOI:
10.1371/journal.ppat.1010193.s019
DOI:
10.1371/journal.ppat.1010193.s020
DOI:
10.1371/journal.ppat.1010193.s021
DOI:
10.1371/journal.ppat.1010193.s022
DOI:
10.1371/journal.ppat.1010193.r001
DOI:
10.1371/journal.ppat.1010193.r002
DOI:
10.1371/journal.ppat.1010193.r003
DOI:
10.1371/journal.ppat.1010193.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
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