Reduced levels of IE2 gene expression and shutdown of early and late viral genes during latent infection of the glioblastoma cell line U138-MG with selectable recombinants of human cytomegalovirus
- PMID: 8091645
- DOI: 10.1006/viro.1994.1514
Reduced levels of IE2 gene expression and shutdown of early and late viral genes during latent infection of the glioblastoma cell line U138-MG with selectable recombinants of human cytomegalovirus
Abstract
To establish stable culture conditions which support persistence of the human cytomegalovirus (HCMV) genome in a latent state, the expression of the bacterial neomycin phosphotransferase (neo) from HCMV recombinants was used for selection. Different cell lines were infected with HCMV recombinants. The human glioblastoma line U138-MG was rendered resistant to G418 and retained the viral genome. More than 90% of the cells expressed the viral IE1 protein of 72 kDa for a culture period of 18 months. Many fewer cells expressed IE2-encoded proteins. No late gene expression or infectious virus was detectable. IE2 gene expression in latently infected cells appeared to be restricted at the level of RNA accumulation. Treatment with TPA or retinoic acid led to enhanced expression of the IE2 gene and the early genes encoding pp65 (UL83) and p52 (UL44). Superinfection with wild-type HCMV led to replication of neo-recombinant virus, indicating that replication-competent virus had been retained in latently infected U138-MG and that the cells had kept their permissive phenotype. Latent HCMV infection in U138-MG cells provides a useful model system for studying the role of particular viral and cellular genes in latent and permissive infections.
Similar articles
-
The human cytomegalovirus IE2 86 kDa protein elevates p53 levels and transactivates the p53 promoter in human fibroblasts.Cell Mol Biol (Noisy-le-grand). 1998 Mar;44(2):321-31. Cell Mol Biol (Noisy-le-grand). 1998. PMID: 9593583
-
Disruption of PML-associated nuclear bodies by IE1 correlates with efficient early stages of viral gene expression and DNA replication in human cytomegalovirus infection.Virology. 2000 Aug 15;274(1):39-55. doi: 10.1006/viro.2000.0448. Virology. 2000. PMID: 10936087
-
Human cytomegalovirus immediate-early gene 2 expression leads to JCV replication in nonpermissive cells via transcriptional activation of JCV T antigen.Virology. 2000 Sep 30;275(2):323-34. doi: 10.1006/viro.2000.0503. Virology. 2000. PMID: 10998333
-
Coordination of late gene transcription of human cytomegalovirus with viral DNA synthesis: recombinant viruses as potential therapeutic vaccine candidates.Expert Opin Ther Targets. 2013 Feb;17(2):157-66. doi: 10.1517/14728222.2013.740460. Epub 2012 Dec 12. Expert Opin Ther Targets. 2013. PMID: 23231449 Review.
-
Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function.Viruses. 2020 Jan 16;12(1):110. doi: 10.3390/v12010110. Viruses. 2020. PMID: 31963209 Free PMC article. Review.
Cited by
-
Cytomegalovirus-mediated induction of antisense mRNA expression to UL44 inhibits virus replication in an astrocytoma cell line: identification of an essential gene.J Virol. 1995 Apr;69(4):2047-57. doi: 10.1128/JVI.69.4.2047-2057.1995. J Virol. 1995. PMID: 7884850 Free PMC article.
-
Recombinant viruses as tools to study human cytomegalovirus immune modulation.Med Microbiol Immunol. 2008 Jun;197(2):215-22. doi: 10.1007/s00430-008-0083-4. Epub 2008 Feb 27. Med Microbiol Immunol. 2008. PMID: 18301917 Review.
-
Retinoid activation of retinoic acid receptors but not of retinoid X receptors promotes cellular differentiation and replication of human cytomegalovirus in embryonal cells.J Virol. 1995 Jun;69(6):3831-7. doi: 10.1128/JVI.69.6.3831-3837.1995. J Virol. 1995. PMID: 7745731 Free PMC article.
-
Molecular modelling of the HCMV IL-10 protein isoforms and analysis of their interaction with the human IL-10 receptor.PLoS One. 2022 Nov 28;17(11):e0277953. doi: 10.1371/journal.pone.0277953. eCollection 2022. PLoS One. 2022. PMID: 36441804 Free PMC article.
-
Ligand induction of retinoic acid receptors alters an acute infection by murine cytomegalovirus.J Virol. 1998 Jun;72(6):4589-600. doi: 10.1128/JVI.72.6.4589-4600.1998. J Virol. 1998. PMID: 9573222 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources