QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 14, Issue 10, 4162-4172, October 2003

This Article Full Text Full Text (PDF) All Versions of this Article: E03-03-0139v1 14/10/4162    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Colón-Ramos, D. A. Articles by Kornbluth, S. Search for Related Content PubMed PubMed Citation Articles by Colón-Ramos, D. A. Articles by Kornbluth, S.

Inhibition of Translation and Induction of Apoptosis by Bunyaviral Nonstructural Proteins Bearing Sequence Similarity to Reaper

Daniel A. Colón-Ramos ^*, Pablo M. Irusta , Eugene C. Gan ^*, Michael R. Olson ^*, Jaewhan Song , Richard I. Morimoto , Richard M. Elliott , Mark Lombard ^¶, Robert Hollingsworth ^¶, J. Marie Hardwick , Gary K. Smith ^¶, and Sally Kornbluth ^* ||

^* Department of Pharmacology and Cancer Biology, C370 LSRC, Duke University Medical Center, Durham, North Carolina 27710; Departments of Pharmacology and Molecular Sciences, Johns Hopkins University Schools of Medicine and Public Health, Baltimore, Maryland 21205; Rice Institute for Biomedical Research, Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208; Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 5JR, Scotland, United Kingdom; and ^¶ GlaxoSmithKline, Research Triangle Park, North Carolina 27709

Submitted March 7, 2003; Revised May 26, 2003; Accepted May 27, 2003
Monitoring Editor: Tony Hunter

Members of the California serogroup of bunyaviruses (family Bunyaviridae) are the leading cause of pediatric viral encephalitis in North America. Significant cell death is observed as part of the infection pathology. We now report that a Bunyaviral nonstructural protein termed NSs shows sequence similarity to Reaper, a proapoptotic protein from Drosophila. Although NSs proteins lack the Reaper N-terminal motif critical for IAP inhibition, they do retain other functions of Reaper that map to conserved C-terminal regions. Like Reaper, NSs proteins induce mitochondrial cytochrome c release and caspase activation in cell-free extracts and promote neuronal apoptosis and mortality in a mouse model. Independent of caspase activation, Bunyavirus NSs proteins also share with Reaper the ability to directly inhibit cellular protein translation. We have found that the shared capacity to inhibit translation and induce apoptosis resides in common sequence motifs present in both Reaper and NSs proteins. Data presented here suggest that NSs induce apoptosis through a mechanism similar to that used by Reaper, as both proteins bind to an apoptotic regulator called Scythe and can relieve Scythe inhibition of Hsp70. Thus, bunyavirus NSs proteins have multiple Reaper-like functions that likely contribute to viral pathogenesis by promoting cell death and/or inhibiting cellular translation.

^|| Corresponding author. E-mail address: kornb001{at}mc.duke.edu.

This article has been cited by other articles:

				G. Blakqori, I. van Knippenberg, and R. M. Elliott Bunyamwera Orthobunyavirus S-Segment Untranslated Regions Mediate Poly(A) Tail-Independent Translation J. Virol., April 15, 2009; 83(8): 3637 - 3646. [Abstract] [Full Text] [PDF]

				E. J. Bartlett, A.-M. Cruz, J. Esker, A. Castano, H. Schomacker, S. R. Surman, M. Hennessey, J. Boonyaratanakornkit, R. J. Pickles, P. L. Collins, et al. Human Parainfluenza Virus Type 1 C Proteins Are Nonessential Proteins That Inhibit the Host Interferon and Apoptotic Responses and Are Required for Efficient Replication in Nonhuman Primates J. Virol., September 15, 2008; 82(18): 8965 - 8977. [Abstract] [Full Text] [PDF]

				E. W. Settles and P. D. Friesen Flock House Virus Induces Apoptosis by Depletion of Drosophila Inhibitor-of-Apoptosis Protein DIAP1 J. Virol., February 1, 2008; 82(3): 1378 - 1388. [Abstract] [Full Text] [PDF]

				C. D. Freel, D. A. Richardson, M. J. Thomenius, E. C. Gan, S. R. Horn, M. R. Olson, and S. Kornbluth Mitochondrial Localization of Reaper to Promote Inhibitors of Apoptosis Protein Degradation Conferred by GH3 Domain-Lipid Interactions J. Biol. Chem., January 4, 2008; 283(1): 367 - 379. [Abstract] [Full Text] [PDF]

				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]

				G. Blakqori, S. Delhaye, M. Habjan, C. D. Blair, I. Sanchez-Vargas, K. E. Olson, G. Attarzadeh-Yazdi, R. Fragkoudis, A. Kohl, U. Kalinke, et al. La Crosse Bunyavirus Nonstructural Protein NSs Serves To Suppress the Type I Interferon System of Mammalian Hosts J. Virol., May 15, 2007; 81(10): 4991 - 4999. [Abstract] [Full Text] [PDF]

				T. Sasaki, E. C. Gan, A. Wakeham, S. Kornbluth, T. W. Mak, and H. Okada HLA-B-associated transcript 3 (Bat3)/Scythe is essential for p300-mediated acetylation of p53 Genes & Dev., April 1, 2007; 21(7): 848 - 861. [Abstract] [Full Text] [PDF]

				G. Kroemer, L. Galluzzi, and C. Brenner Mitochondrial Membrane Permeabilization in Cell Death Physiol Rev, January 1, 2007; 87(1): 99 - 163. [Abstract] [Full Text] [PDF]

				A. Boyd, J. K. Fazakerley, and A. Bridgen Pathogenesis of Dugbe virus infection in wild-type and interferon-deficient mice J. Gen. Virol., July 1, 2006; 87(7): 2005 - 2009. [Abstract] [Full Text] [PDF]

				J. Liu, I. Chen, Q. Du, H. Chua, and J. Kwang The ORF3 Protein of Porcine Circovirus Type 2 Is Involved in Viral Pathogenesis In Vivo. J. Virol., May 1, 2006; 80(10): 5065 - 5073. [Abstract] [Full Text] [PDF]

				G. Blakqori and F. Weber Efficient cDNA-Based Rescue of La Crosse Bunyaviruses Expressing or Lacking the Nonstructural Protein NSs J. Virol., August 15, 2005; 79(16): 10420 - 10428. [Abstract] [Full Text] [PDF]

				I. Ivanovska and J. M. Hardwick Viruses activate a genetically conserved cell death pathway in a unicellular organism J. Cell Biol., August 1, 2005; 170(3): 391 - 399. [Abstract] [Full Text] [PDF]

				T. Ikegami, C. J. Peters, and S. Makino Rift Valley Fever Virus Nonstructural Protein NSs Promotes Viral RNA Replication and Transcription in a Minigenome System J. Virol., May 1, 2005; 79(9): 5606 - 5615. [Abstract] [Full Text] [PDF]

				S. S. Soldan, M. L. Plassmeyer, M. K. Matukonis, and F. Gonzalez-Scarano La Crosse Virus Nonstructural Protein NSs Counteracts the Effects of Short Interfering RNA J. Virol., January 1, 2005; 79(1): 234 - 244. [Abstract] [Full Text] [PDF]

				D. Thomas, G. Blakqori, V. Wagner, M. Banholzer, N. Kessler, R. M. Elliott, O. Haller, and F. Weber Inhibition of RNA Polymerase II Phosphorylation by a Viral Interferon Antagonist J. Biol. Chem., July 23, 2004; 279(30): 31471 - 31477. [Abstract] [Full Text] [PDF]