| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Virology, Division of Investigative Science, Imperial College Faculty of Medicine, St Mary's Campus, Norfolk Place, London W2 1PG, UK
2 Max von Pettenkofer Institut, Abteilung für Virologie, LMU-München, Germany
Correspondence
Richard F. Greaves
richard.greaves{at}imperial.ac.uk
Gabriele Hahn
ghahn{at}m3401.mpk.med.uni-muenchen.de
Human cytomegalovirus (HCMV) strain AD169 mutants carrying transposon insertions or large deletions in UL37 exon 1 (UL37x1) were recovered from modified bacterial artificial chromosomes by reconstitution in human fibroblasts expressing the adenovirus anti-apoptotic protein E1B19K. UL37x1 mutant growth was severely compromised in normal fibroblasts, with minimal release of infectious progeny. Growth in E1B19K-expressing cells was restored, but did not reach wild-type levels. Normal fibroblasts infected by UL37x1 mutants underwent apoptosis spontaneously between 48 and 96 h after infection. Apoptosis was inhibited by treatment of cells with the broad-spectrum caspase inhibitor z-Val-Ala-Asp(OMe)-fluoromethylketone, resulting in substantially increased release of virus. Inhibition of viral DNA replication by phosphonoformate or ganciclovir also inhibited apoptosis, implying that death was triggered by late viral functions or by replication and packaging of the viral genome. Immunofluorescent staining showed that although viral proteins accumulated normally during delayed-early phase and viral DNA replication compartments formed, viral late proteins were detected only rarely, suggesting that spontaneous apoptosis occurs early in late phase. These results demonstrate that anti-apoptotic proteins encoded by HCMV UL37x1 [pUL37x1 (vMIA), gpUL37 and gpUL37M] prevent apoptosis that would otherwise be initiated by the replication programme of the virus and are required for efficient and sustainable virus replication.
Present address: Division of Hepatology and Gene Therapy, Department of Internal Medicine, University of Navarra, Pamplona, Spain.
This article has been cited by other articles:
|
|
 |
|
  M. C.-J. Cheeran, J. R. Lokensgard, and M. R. Schleiss Neuropathogenesis of Congenital Cytomegalovirus Infection: Disease Mechanisms and Prospects for Intervention Clin. Microbiol. Rev., January 1, 2009; 22(1): 99 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Jurak, U. Schumacher, H. Simic, S. Voigt, and W. Brune Murine Cytomegalovirus m38.5 Protein Inhibits Bax-Mediated Cell Death J. Virol., May 15, 2008; 82(10): 4812 - 4822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Bozidis, C. D. Williamson, and A. M. Colberg-Poley Mitochondrial and Secretory Human Cytomegalovirus UL37 Proteins Traffic into Mitochondrion-Associated Membranes of Human Cells J. Virol., March 15, 2008; 82(6): 2715 - 2726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Cicin-Sain, Z. Ruzsics, J. Podlech, I. Bubic, C. Menard, S. Jonjic, M. J. Reddehase, and U. H. Koszinowski Dominant-Negative FADD Rescues the In Vivo Fitness of a Cytomegalovirus Lacking an Antiapoptotic Viral Gene J. Virol., March 1, 2008; 82(5): 2056 - 2064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Reeves, A. A. Davies, B. P. McSharry, G. W. Wilkinson, and J. H. Sinclair Complex I Binding by a Virally Encoded RNA Regulates Mitochondria-Induced Cell Death Science, June 1, 2007; 316(5829): 1345 - 1348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Terhune, E. Torigoi, N. Moorman, M. Silva, Z. Qian, T. Shenk, and D. Yu Human Cytomegalovirus UL38 Protein Blocks Apoptosis J. Virol., April 1, 2007; 81(7): 3109 - 3123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Jarvis and J. A. Nelson Human Cytomegalovirus Tropism for Endothelial Cells: Not All Endothelial Cells Are Created Equal J. Virol., March 1, 2007; 81(5): 2095 - 2101. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Sharon-Friling, J. Goodhouse, A. M. Colberg-Poley, and T. Shenk Human cytomegalovirus pUL37x1 induces the release of endoplasmic reticulum calcium stores PNAS, December 12, 2006; 103(50): 19117 - 19122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Poncet, A.-L. Pauleau, G. Szabadkai, A. Vozza, S. R. Scholz, M. Le Bras, J.-J. Briere, A. Jalil, R. Le Moigne, C. Brenner, et al. Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA J. Cell Biol., September 25, 2006; 174(7): 985 - 996. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Odeberg, N. Wolmer, S. Falci, M. Westgren, A. Seiger, and C. Soderberg-Naucler Human cytomegalovirus inhibits neuronal differentiation and induces apoptosis in human neural precursor cells. J. Virol., September 1, 2006; 80(18): 8929 - 8939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Mavinakere, C. D. Williamson, V. S. Goldmacher, and A. M. Colberg-Poley Processing of Human Cytomegalovirus UL37 Mutant Glycoproteins in the Endoplasmic Reticulum Lumen prior to Mitochondrial Importation J. Virol., July 15, 2006; 80(14): 6771 - 6783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Utama, Y. H. Shen, B. M. Mitchell, I. T. Makagiansar, Y. Gan, R. Muthuswamy, S. Duraisamy, D. Martin, X. Wang, M.-X. Zhang, et al. Mechanisms for human cytomegalovirus-induced cytoplasmic p53 sequestration in endothelial cells J. Cell Sci., June 15, 2006; 119(12): 2457 - 2467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. B. Smith and E. S. Mocarski Contribution of GADD45 Family Members to Cell Death Suppression by Cellular Bcl-xL and Cytomegalovirus vMIA J. Virol., December 1, 2005; 79(23): 14923 - 14932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. T. Wasilenko, L. Banadyga, D. Bond, and M. Barry The Vaccinia Virus F1L Protein Interacts with the Proapoptotic Protein Bak and Inhibits Bak Activation J. Virol., November 15, 2005; 79(22): 14031 - 14043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. McCormick, C. D. Meiering, G. B. Smith, and E. S. Mocarski Mitochondrial Cell Death Suppressors Carried by Human and Murine Cytomegalovirus Confer Resistance to Proteasome Inhibitor-Induced Apoptosis J. Virol., October 1, 2005; 79(19): 12205 - 12217. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| INT J SYST EVOL MICROBIOL | MICROBIOLOGY | J GEN VIROL |
| J MED MICROBIOL | ALL SGM JOURNALS | |
