Yeast two-hybrid screening service Sign up for PNAS Online eTocs
Link: Info for AuthorsLink: Editorial BoardLink: AboutLink: SubscribeLink: AdvertiseLink: ContactLink: Sitemap Link: PNAS Home
Proceedings of the National Academy of Sciences
Link: Current Issue "" Link: Archives "" Link: Online Submission ""  Link: Advanced Search

Published online on June 26, 2001, 10.1073/pnas.141108798

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Skaletskaya, A.
Right arrow Articles by Goldmacher, V. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Skaletskaya, A.
Right arrow Articles by Goldmacher, V. S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg  
What's this?

Cell Biology
 A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8 activation

Anna Skaletskaya*, Laura M. Bartle*, Thomas Chittenden*, A. Louise McCormickdagger , Edward S. Mocarskidagger , and Victor S. Goldmacher*,Dagger

* ImmunoGen, 128 Sidney Street, Cambridge, MA 02139; and dagger  Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305

Edited by Bernard Roizman, University of Chicago, Chicago, IL, and approved May 16, 2001 (received for review March 5, 2001)

We have identified a human cytomegalovirus cell-death suppressor, denoted vICA, encoded by the viral UL36 gene. vICA inhibits Fas-mediated apoptosis by binding to the pro-domain of caspase-8 and preventing its activation. vICA does not share significant sequence homology with FLIPs or other known suppressors of apoptosis, suggesting that this protein represents a new class of cell-death suppressors. Notably, resistance to Fas-mediated apoptosis is delayed in fibroblasts infected with viruses that encode mutant vICA, suggesting that vICA suppresses death-receptor-induced cell death in the context of viral infection. Although vICA is dispensable for viral replication in vitro, the common targeting of caspase-8 activation by diverse herpesviruses argues for an important role for this antiapoptotic mechanism in the pathogenesis of viral infection in the host, most likely in avoiding immune clearance by cytotoxic lymphocytes and natural killer cells.

Dagger To whom reprint requests should be addressed. E-mail: victor.goldmacher{at}immunogen.com.

www.pnas.org/cgi/doi/10.1073/pnas.141108798
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg    What's this?


This article has been cited by other articles in HighWire Press-hosted journals:


Home page
 J. Virol.Home page
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]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. Mack, A. Sickmann, D. Lembo, and W. Brune
Inhibition of proinflammatory and innate immune signaling pathways by a cytomegalovirus RIP1-interacting protein
PNAS, February 26, 2008; 105(8): 3094 - 3099.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
M. Mandron, H. Martin, B. Bonjean, J. Lule, E. Tartour, and C. Davrinche
Dendritic cell-induced apoptosis of human cytomegalovirus-infected fibroblasts promotes cross-presentation of pp65 to CD8+ T cells
J. Gen. Virol., January 1, 2008; 89(1): 78 - 86.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
J. A. Nelson
Small RNAs and Large DNA Viruses
N. Engl. J. Med., December 20, 2007; 357(25): 2630 - 2632.
[Full Text] [PDF]

Home page
 J. Virol.Home page
S. Won, T. Ikegami, C. J. Peters, and S. Makino
NSm Protein of Rift Valley Fever Virus Suppresses Virus-Induced Apoptosis
J. Virol., December 15, 2007; 81(24): 13335 - 13345.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
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]

Home page
 J. Virol.Home page
M. Filippova, M. M. Johnson, M. Bautista, V. Filippov, N. Fodor, S. S. Tungteakkhun, K. Williams, and P. J. Duerksen-Hughes
The Large and Small Isoforms of Human Papillomavirus Type 16 E6 Bind to and Differentially Affect Procaspase 8 Stability and Activity
J. Virol., April 15, 2007; 81(8): 4116 - 4129.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
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]

Home page
 J. Virol.Home page
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]

Home page
 J. Immunol.Home page
S.-H. Chiou, Y.-P. Yang, J.-C. Lin, C.-H. Hsu, H.-C. Jhang, Y.-T. Yang, C.-H. Lee, L. L. T. Ho, W.-M. Hsu, H.-H. Ku, et al.
The Immediate Early 2 Protein of Human Cytomegalovirus (HCMV) Mediates the Apoptotic Control in HCMV Retinitis through Up-Regulation of the Cellular FLICE-Inhibitory Protein Expression
J. Immunol., November 1, 2006; 177(9): 6199 - 6206.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
R. S. Valchanova, M. Picard-Maureau, M. Budt, and W. Brune
Murine Cytomegalovirus m142 and m143 Are both Required To Block Protein Kinase R-Mediated Shutdown of Protein Synthesis.
J. Virol., October 1, 2006; 80(20): 10181 - 10190.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
X. Feng, J. Schroer, D. Yu, and T. Shenk
Human Cytomegalovirus pUS24 Is a Virion Protein That Functions Very Early in the Replication Cycle.
J. Virol., September 1, 2006; 80(17): 8371 - 8378.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
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]

Home page
 J. Virol.Home page
K. Lorz, H. Hofmann, A. Berndt, N. Tavalai, R. Mueller, U. Schlotzer-Schrehardt, and T. Stamminger
Deletion of Open Reading Frame UL26 from the Human Cytomegalovirus Genome Results in Reduced Viral Growth, Which Involves Impaired Stability of Viral Particles.
J. Virol., June 1, 2006; 80(11): 5423 - 5434.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
Z. Zhang, D. L. Evers, J. F. McCarville, J.-C. Dantonel, S.-M. Huong, and E.-S. Huang
Evidence that the Human Cytomegalovirus IE2-86 Protein Binds mdm2 and Facilitates mdm2 Degradation.
J. Virol., April 1, 2006; 80(8): 3833 - 3843.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
M.-Y. Park, Y.-E. Kim, M.-R. Seo, J.-R. Lee, C. H. Lee, and J.-H. Ahn
Interactions among Four Proteins Encoded by the Human Cytomegalovirus UL112-113 Region Regulate Their Intranuclear Targeting and the Recruitment of UL44 to Prereplication Foci
J. Virol., March 15, 2006; 80(6): 2718 - 2727.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
A. Iannello, O. Debbeche, E. Martin, L. H. Attalah, S. Samarani, and A. Ahmad
Viral strategies for evading antiviral cellular immune responses of the host
J. Leukoc. Biol., January 1, 2006; 79(1): 16 - 35.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
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]

Home page
 J. Virol.Home page
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 page
 J. Virol.Home page
E. A. White and D. H. Spector
Exon 3 of the Human Cytomegalovirus Major Immediate-Early Region Is Required for Efficient Viral Gene Expression and for Cellular Cyclin Modulation
J. Virol., June 15, 2005; 79(12): 7438 - 7452.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Terrasson, S. Allart, H. Martin, J. Lule, H. Haddada, D. Caput, and C. Davrinche
p73-Dependent Apoptosis through Death Receptor: Impairment by Human Cytomegalovirus Infection
Cancer Res., April 1, 2005; 65(7): 2787 - 2794.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
Z. Karabekian, L. K. Hanson, J. S. Slater, N. K. Krishna, L. L. Bolin, J. A. Kerry, and A. E. Campbell
Complex Formation among Murine Cytomegalovirus US22 Proteins Encoded by Genes M139, M140, and M141
J. Virol., March 15, 2005; 79(6): 3525 - 3535.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
B. Oster, B. Bundgaard, and P. Hollsberg
Human Herpesvirus 6B Induces Cell Cycle Arrest Concomitant with p53 Phosphorylation and Accumulation in T Cells
J. Virol., February 1, 2005; 79(3): 1961 - 1965.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
M. Reboredo, R. F. Greaves, and G. Hahn
Human cytomegalovirus proteins encoded by UL37 exon 1 protect infected fibroblasts against virus-induced apoptosis and are required for efficient virus replication
J. Gen. Virol., December 1, 2004; 85(12): 3555 - 3567.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
Y. Xu, S. A. Cei, A. Rodriguez Huete, K. S. Colletti, and G. S. Pari
Human Cytomegalovirus DNA Replication Requires Transcriptional Activation via an IE2- and UL84-Responsive Bidirectional Promoter Element within oriLyt
J. Virol., November 1, 2004; 78(21): 11664 - 11677.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
L. Hertel and E. S. Mocarski
Global Analysis of Host Cell Gene Expression Late during Cytomegalovirus Infection Reveals Extensive Dysregulation of Cell Cycle Gene Expression and Induction of Pseudomitosis Independent of US28 Function
J. Virol., November 1, 2004; 78(21): 11988 - 12011.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
D. A. Abate, S. Watanabe, and E. S. Mocarski
Major Human Cytomegalovirus Structural Protein pp65 (ppUL83) Prevents Interferon Response Factor 3 Activation in the Interferon Response
J. Virol., October 15, 2004; 78(20): 10995 - 11006.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Biol.Home page
C. E. Andoniou, D. M. Andrews, M. Manzur, P. Ricciardi-Castagnoli, and M. A. Degli-Esposti
A novel checkpoint in the Bcl-2-regulated apoptotic pathway revealed by murine cytomegalovirus infection of dendritic cells
J. Cell Biol., September 13, 2004; 166(6): 827 - 837.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Filippova, L. Parkhurst, and P. J. Duerksen-Hughes
The Human Papillomavirus 16 E6 Protein Binds to Fas-associated Death Domain and Protects Cells from Fas-triggered Apoptosis
J. Biol. Chem., June 11, 2004; 279(24): 25729 - 25744.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. Arnoult, L. M. Bartle, A. Skaletskaya, D. Poncet, N. Zamzami, P. U. Park, J. Sharpe, R. J. Youle, and V. S. Goldmacher
Cytomegalovirus cell death suppressor vMIA blocks Bax- but not Bak-mediated apoptosis by binding and sequestering Bax at mitochondria
PNAS, May 25, 2004; 101(21): 7988 - 7993.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
A. Dolan, C. Cunningham, R. D. Hector, A. F. Hassan-Walker, L. Lee, C. Addison, D. J. Dargan, D. J. McGeoch, D. Gatherer, V. C. Emery, et al.
Genetic content of wild-type human cytomegalovirus
J. Gen. Virol., May 1, 2004; 85(5): 1301 - 1312.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
B. Slobedman, J. L. Stern, A. L. Cunningham, A. Abendroth, D. A. Abate, and E. S. Mocarski
Impact of Human Cytomegalovirus Latent Infection on Myeloid Progenitor Cell Gene Expression
J. Virol., April 15, 2004; 78(8): 4054 - 4062.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
M. S. Mavinakere and A. M. Colberg-Poley
Dual targeting of the human cytomegalovirus UL37 exon 1 protein during permissive infection
J. Gen. Virol., February 1, 2004; 85(2): 323 - 329.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
M. Patrone, E. Percivalle, M. Secchi, L. Fiorina, G. Pedrali-Noy, M. Zoppe, F. Baldanti, G. Hahn, U. H. Koszinowski, G. Milanesi, et al.
The human cytomegalovirus UL45 gene product is a late, virion-associated protein and influences virus growth at low multiplicities of infection
J. Gen. Virol., December 1, 2003; 84(12): 3359 - 3370.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
Y. Su, R. Adair, C. N. Davis, N. L. DiFronzo, and A. M. Colberg-Poley
Convergence of RNA cis Elements and Cellular Polyadenylation Factors in the Regulation of Human Cytomegalovirus UL37 Exon 1 Unspliced RNA Production
J. Virol., December 1, 2003; 77(23): 12729 - 12741.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
C. Hood, A. L. Cunningham, B. Slobedman, R. A. Boadle, and A. Abendroth
Varicella-Zoster Virus-Infected Human Sensory Neurons Are Resistant to Apoptosis, yet Human Foreskin Fibroblasts Are Susceptible: Evidence for a Cell-Type-Specific Apoptotic Response
J. Virol., December 1, 2003; 77(23): 12852 - 12864.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
W. Brune, M. Nevels, and T. Shenk
Murine Cytomegalovirus m41 Open Reading Frame Encodes a Golgi-Localized Antiapoptotic Protein
J. Virol., November 1, 2003; 77(21): 11633 - 11643.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
K. Kondo, H. Nozaki, K. Shimada, and K. Yamanishi
Detection of a Gene Cluster That Is Dispensable for Human Herpesvirus 6 Replication and Latency
J. Virol., October 1, 2003; 77(19): 10719 - 10724.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
L. Hertel, V. G. Lacaille, H. Strobl, E. D. Mellins, and E. S. Mocarski
Susceptibility of Immature and Mature Langerhans Cell-Type Dendritic Cells to Infection and Immunomodulation by Human Cytomegalovirus
J. Virol., July 1, 2003; 77(13): 7563 - 7574.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
S. G. Hansen, L. I. Strelow, D. C. Franchi, D. G. Anders, and S. W. Wong
Complete Sequence and Genomic Analysis of Rhesus Cytomegalovirus
J. Virol., June 15, 2003; 77(12): 6620 - 6636.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
C. Menard, M. Wagner, Z. Ruzsics, K. Holak, W. Brune, A. E. Campbell, and U. H. Koszinowski
Role of Murine Cytomegalovirus US22 Gene Family Members in Replication in Macrophages
J. Virol., May 15, 2003; 77(10): 5557 - 5570.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
Y. Su, J. R. Testaverde, C. N. Davis, W. A. Hayajneh, R. Adair, and A. M. Colberg-Poley
Human cytomegalovirus UL37 immediate early target minigene RNAs are accurately spliced and polyadenylated
J. Gen. Virol., January 1, 2003; 84(1): 29 - 39.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
A. L. McCormick, V. L. Smith, D. Chow, and E. S. Mocarski
Disruption of Mitochondrial Networks by the Human Cytomegalovirus UL37 Gene Product Viral Mitochondrion-Localized Inhibitor of Apoptosis
J. Virol., December 6, 2002; 77(1): 631 - 641.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
Y. Langelier, S. Bergeron, S. Chabaud, J. Lippens, C. Guilbault, A. M.-J. Sasseville, S. Denis, D. D. Mosser, and B. Massie
The R1 subunit of herpes simplex virus ribonucleotide reductase protects cells against apoptosis at, or upstream of, caspase-8 activation
J. Gen. Virol., November 1, 2002; 83(11): 2779 - 2789.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
E. Noris, C. Zannetti, A. Demurtas, J. Sinclair, M. De Andrea, M. Gariglio, and S. Landolfo
Cell Cycle Arrest by Human Cytomegalovirus 86-kDa IE2 Protein Resembles Premature Senescence
J. Virol., October 25, 2002; 76(23): 12135 - 12148.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
G. Hahn, H. Khan, F. Baldanti, U. H. Koszinowski, M. G. Revello, and G. Gerna
The Human Cytomegalovirus Ribonucleotide Reductase Homolog UL45 Is Dispensable for Growth in Endothelial Cells, as Determined by a BAC-Cloned Clinical Isolate of Human Cytomegalovirus with Preserved Wild-Type Characteristics
J. Virol., August 12, 2002; 76(18): 9551 - 9555.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Allart, H. Martin, C. Detraves, J. Terrasson, D. Caput, and C. Davrinche
Human Cytomegalovirus Induces Drug Resistance and Alteration of Programmed Cell Death by Accumulation of Delta N-p73alpha
J. Biol. Chem., August 2, 2002; 277(32): 29063 - 29068.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
E. Le Roy, M. Baron, W. Faigle, D. Clement, D. M. Lewinsohn, D. N. Streblow, J. A. Nelson, S. Amigorena, and J.-L. Davignon
Infection of APC by Human Cytomegalovirus Controlled Through Recognition of Endogenous Nuclear Immediate Early Protein 1 by Specific CD4+ T Lymphocytes
J. Immunol., August 1, 2002; 169(3): 1293 - 1301.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
Y. Xu, K. S. Colletti, and G. S. Pari
Human Cytomegalovirus UL84 Localizes to the Cell Nucleus via a Nuclear Localization Signal and Is a Component of Viral Replication Compartments
J. Virol., July 29, 2002; 76(17): 8931 - 8938.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
R. Adair, E. R. Douglas, J. B. Maclean, S. Y. Graham, J. D. Aitken, F. E. Jamieson, and D. J. Dargan
The products of human cytomegalovirus genes UL23, UL24, UL43 and US22 are tegument components
J. Gen. Virol., June 1, 2002; 83(6): 1315 - 1324.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
S. Hay and G. Kannourakis
A time to kill: viral manipulation of the cell death program
J. Gen. Virol., June 1, 2002; 83(7): 1547 - 1564.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
T. Stamminger, M. Gstaiger, K. Weinzierl, K. Lorz, M. Winkler, and W. Schaffner
Open Reading Frame UL26 of Human Cytomegalovirus Encodes a Novel Tegument Protein That Contains a Strong Transcriptional Activation Domain
J. Virol., April 16, 2002; 76(10): 4836 - 4847.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S.-H. Chiou, J.-H. Liu, W.-M. Hsu, S. S.-L. Chen, S.-Y. Chang, L.-J. Juan, J.-C. Lin, Y.-T. Yang, W.-W. Wong, C.-Y. Liu, et al.
Up-Regulation of Fas Ligand Expression by Human Cytomegalovirus Immediate-Early Gene Product 2: A Novel Mechanism in Cytomegalovirus-Induced Apoptosis in Human Retina
J. Immunol., October 1, 2001; 167(7): 4098 - 4103.
[Abstract] [Full Text] [PDF]