The human cytomegalovirus UL133-138 gene locus attenuates the lytic viral cycle in fibroblasts

Nirmal Dutta; Philip Lashmit; Jinxiang Yuan; Jeffery Meier; Mark F Stinski

doi:10.1371/journal.pone.0120946

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The human cytomegalovirus UL133-138 gene locus attenuates the lytic viral cycle in fibroblasts

Journal article

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Peer reviewed

The human cytomegalovirus UL133-138 gene locus attenuates the lytic viral cycle in fibroblasts

Nirmal Dutta, Philip Lashmit, Jinxiang Yuan, Jeffery Meier and Mark F Stinski

PloS one, Vol.10(3), pp.e0120946-e0120946

2015

DOI: 10.1371/journal.pone.0120946

PMCID: PMC4370700

PMID: 25799165

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Abstract

The genomes of HCMV clinical strains (e.g. FIX, TR, PH, etc) contain a 15 kb region that encodes 20 putative ORFs. The region, termed ULb', is lost after serial passage of virus in human foreskin fibroblast (HFF) cell culture. Compared to clinical strains, laboratory strains replicate faster and to higher titers of infectious virus. We made recombinant viruses with 22, 14, or 7 ORFs deleted from the ULb' region using FIX and TR as model clinical strains. We also introduced a stop codon into single ORFs between UL133 and UL138 to prevent protein expression. All deletions within ULb' and all stop codon mutants within the UL133 to UL138 region increased to varying degrees, viral major immediate early RNA and protein, DNA, and cell-free infectious virus compared to the wild type viruses. The wild type viral proteins slowed down the viral replication process along with cell-free infectious virus release from human fibroblast cells.

Fibroblasts - virology

Cytomegalovirus - genetics

Genome, Viral

Gene Expression

Virus Replication - genetics

Humans

Open Reading Frames

Cells, Cultured

Viral Proteins - genetics

DNA Replication

Recombination, Genetic

Gene Deletion

Transcription, Genetic

Genes, Immediate-Early

Mutation

Codon, Terminator

DNA, Viral

Gene Order

Details

Title: Subtitle: The human cytomegalovirus UL133-138 gene locus attenuates the lytic viral cycle in fibroblasts
Creators: Nirmal Dutta - Department of Internal Medicine, University of Iowa, Iowa City, United States of America
Philip Lashmit - Center for Biocatalysis and Bioprocessing, University of Iowa, Iowa City, United States of America
Jinxiang Yuan - Department of Internal Medicine, University of Iowa, Iowa City, United States of America
Jeffery Meier - Department of Internal Medicine, University of Iowa, Iowa City, United States of America; Iowa Veterans Affairs Healthcare System, Iowa City, United States of America
Mark F Stinski - Department of Microbiology, University of Iowa, Iowa City, United States of America
Resource Type: Journal article
Publication Details: PloS one, Vol.10(3), pp.e0120946-e0120946
DOI: 10.1371/journal.pone.0120946
PMID: 25799165
PMCID: PMC4370700
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science
Grant note: I01 BX001107 / BLRD VA R21 AI013562 / NIAID NIH HHS AI-13562 / NIAID NIH HHS R01 AI013562 / NIAID NIH HHS
Language: English
Date published: 2015
Academic Unit: Microbiology and Immunology; Infectious Diseases; Epidemiology; Center for Biocatalysis and Bioprocessing; Internal Medicine
Record Identifier: 9984094341102771

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