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PMID: 8230421 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

Eleven loci encoding trans-acting factors are required for transient complementation of human cytomegalovirus oriLyt-dependent DNA replication.

Journal of virology ·Vol. 67 ·No. 12 ·1993-12-00 ·Pages 6979-88

Pari GS, Anders DG

Abstract

Recently we described the use of human cytomegalovirus (HCMV) cosmid clones in a cotransfection assay of HCMV oriLyt replication (G. S. Pari, M. A. Kacica, and D. G. Anders, J. Virol. 67:2575-2582, 1993). We have now used this assay to identify 11 distinct required loci encoding trans-acting factors sufficient for transient complementation of oriLyt-dependent DNA replication. This set includes all of the virus genes essential to initiate and perform DNA synthesis together with the virus genes required to express these replication functions from their native promoters. Six of the identified loci span open reading frames (ORFs) that encode homologs or probable homologs of herpes simplex virus type 1 replication genes, consistent with predictions based on sequence similarities and biochemical properties. These include the DNA polymerase UL54 and polymerase-associated protein UL44, the single-stranded-DNA-binding protein UL57, and proposed subunits of a helicase-primase complex, UL70, UL105, and UL101-102. Frameshift mutations in any one of these essential ORFs abrogated complementation of DNA replication. Three required loci, UL36-38, IRS1 (or TRS1), and IE1/IE2, encode known regulatory proteins. The remaining two loci span ORFs UL84 and UL112-113 and encode early temporal class nucleus-associated proteins of unknown function. Neither of these genes have been implicated previously in DNA replication or in regulating gene expression, nor have counterparts in herpes simplex virus type 1 or Epstein-Barr virus been described. The results presented here will facilitate investigation of the mechanisms and regulation of HCMV lytic-phase DNA replication.

MeSH Terms
Cells, Cultured Cloning, Molecular Cosmids Cytomegalovirus/genetics,growth & development DNA Replication Genes, Viral Genetic Complementation Test Herpesviridae/genetics Humans Trans-Activators/genetics,metabolism Transfection Viral Regulatory and Accessory Proteins/genetics,metabolism
Chemicals
Trans-Activators Viral Regulatory and Accessory Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Pari G S
Laboratory of Virology, Wadsworth Center for Laboratories and Research, Albany, New York.
Anders D G
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.67.12.6979-6988.1993
Published
1993-12-00
Pages
6979-88
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC238157
Subset
IM
Grants
NIAID NIH HHS · AI31249 · United States
NIAID NIH HHS · AI33416 · United States
External Links
PubMed source DOI: 10.1128/JVI.67.12.6979-6988.1993 PMC Full Text View journal details
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