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Simian virus 40 T/t antigens and lamin A/C small interfering RNA rescue the phenotype of an Epstein-Barr virus protein kinase (BGLF4) mutant.
- Source :
-
Journal of virology [J Virol] 2010 May; Vol. 84 (9), pp. 4524-33. Date of Electronic Publication: 2010 Feb 10. - Publication Year :
- 2010
-
Abstract
- The Epstein-Barr virus (EBV)-encoded viral protein kinase, EBV-PK (the BGLF4 gene product), is required for efficient nuclear viral egress in 293 cells. However, since EBV-PK phosphorylates a number of different viral and cellular proteins (including lamin A/C), the relative importance of each target during lytic viral replication remains unclear. We show here that an EBV PK mutant (PKmut; containing stop codons at residues 1 and 5 in EBV-PK) is highly defective for release of infectious virus from 293 cells but not 293T cells. Furthermore, the phenotype of the PKmut in 293 cells is substantially reversed by expression of the simian virus 40 (SV40) large (T) and small (t) T antigens. Efficient rescue requires the presence of both SV40 T/t proteins. We show that 293T cells have a much higher level of constitutive lamin A/C phosphorylation than do 293 cells over residues (S22 and S392) that promote phosphorylation-dependent nuclear disassembly and that both large T and small t contribute to enhanced lamin A/C phosphorylation. Finally, we demonstrate that knockdown of lamin A/C expression using small interfering RNA also rescues the PKmut phenotype in 293 cells. These results suggest that essential roles of EBV-PK during lytic viral replication include the phosphorylation and dispersion of lamin A/C.
- Subjects :
- Cell Line
Gene Knockdown Techniques
Herpesvirus 4, Human genetics
Humans
Lamin Type A metabolism
Phosphorylation
RNA, Small Interfering genetics
Simian virus 40
Antigens, Polyomavirus Transforming biosynthesis
Herpesvirus 4, Human growth & development
Host-Pathogen Interactions
Lamin Type A antagonists & inhibitors
Protein Serine-Threonine Kinases deficiency
Protein Serine-Threonine Kinases physiology
Viral Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 84
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 20147387
- Full Text :
- https://doi.org/10.1128/JVI.02456-09