scholarly journals The Fowlpox Virus BCL-2 Homologue, FPV039, Interacts with Activated Bax and a Discrete Subset of BH3-Only Proteins To Inhibit Apoptosis

2009 ◽  
Vol 83 (14) ◽  
pp. 7085-7098 ◽  
Author(s):  
Logan Banadyga ◽  
Kirstin Veugelers ◽  
Stephanie Campbell ◽  
Michele Barry
Keyword(s):  
Sequence Homology ◽  
Cellular Protein ◽  
Virus Protein ◽  
Discrete Subset ◽  
Fowlpox Virus ◽  
Subsequent Formation ◽  
Bh3 Domain ◽  
Induction Of Apoptosis ◽  
Trigger Cell Death ◽  
Canarypox Virus

ABSTRACT Apoptosis is a potent immune barrier against viral infection, and many viruses, including poxviruses, encode proteins to overcome this defense. Interestingly, the avipoxviruses, which include fowlpox and canarypox virus, are the only poxviruses known to encode proteins with obvious Bcl-2 sequence homology. We previously characterized the fowlpox virus protein FPV039 as a Bcl-2-like antiapoptotic protein that inhibits apoptosis by interacting with and inactivating the proapoptotic cellular protein Bak. However, both Bak and Bax can independently trigger cell death. Thus, to effectively inhibit apoptosis, a number of viruses also inhibit Bax. Here we show that FPV039 inhibited apoptosis induced by Bax overexpression and prevented both the conformational activation of Bax and the subsequent formation of Bax oligomers at the mitochondria, two critical steps in the induction of apoptosis. Additionally, FPV039 interacted with activated Bax in the context of Bax overexpression and virus infection. Importantly, the ability of FPV039 to interact with active Bax and inhibit Bax activity was dependent on the structurally conserved BH3 domain of FPV039, even though this domain possesses little sequence homology to other BH3 domains. FPV039 also inhibited apoptosis induced by the BH3-only proteins, upstream activators of Bak and Bax, despite interacting detectably with only two: BimL and Bik. Collectively, our data suggest that FPV039 inhibits apoptosis by sequestering and inactivating multiple proapoptotic Bcl-2 proteins, including certain BH3-only proteins and both of the critical “gatekeepers” of apoptosis, Bak and Bax.

scholarly journals ISG56/IFIT1 is primarily responsible for interferon-induced changes to patterns of parainfluenza virus type 5 transcription and protein synthesis

2013 ◽  
Vol 94 (1) ◽  
pp. 59-68 ◽  
Author(s):  
J. Andrejeva ◽  
H. Norsted ◽  
M. Habjan ◽  
V. Thiel ◽  
S. Goodbourn ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Virus Type ◽  
Cellular Protein ◽  
Parainfluenza Virus ◽  
Hydroxyl Group ◽  
Virus Protein ◽  
Viral Mrnas ◽  
Tetratricopeptide Repeats ◽  
Virus Transcription

Interferon (IFN) induces an antiviral state in cells that results in alterations of the patterns and levels of parainfluenza virus type 5 (PIV5) transcripts and proteins. This study reports that IFN-stimulated gene 56/IFN-induced protein with tetratricopeptide repeats 1 (ISG56/IFIT1) is primarily responsible for these effects of IFN. It was shown that treating cells with IFN after infection resulted in an increase in virus transcription but an overall decrease in virus protein synthesis. As there was no obvious decrease in the overall levels of cellular protein synthesis in infected cells treated with IFN, these results suggested that ISG56/IFIT1 selectively inhibits the translation of viral mRNAs. This conclusion was supported by in vitro translation studies. Previous work has shown that ISG56/IFIT1 can restrict the replication of viruses lacking a 2′-O-methyltransferase activity, an enzyme that methylates the 2′-hydroxyl group of ribose sugars in the 5′-cap structures of mRNA. However, the data in the current study strongly suggested that PIV5 mRNAs are methylated at the 2′-hydroxyl group and thus that ISG56/IFIT1 selectively inhibits the translation of PIV5 mRNA by some as yet unrecognized mechanism. It was also shown that ISG56/IFIT1 is primarily responsible for the IFN-induced inhibition of PIV5.

scholarly journals In Vitro and In Vivo Interactions between the Hepatitis B Virus Protein P22 and the Cellular Protein gC1qR

2003 ◽  
Vol 77 (23) ◽  
pp. 12875-12880 ◽  
Author(s):  
S. Lainé ◽  
A. Thouard ◽  
J. Derancourt ◽  
M. Kress ◽  
D. Sitterlin ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Matrix Protein ◽  
Cellular Protein ◽  
Virus Protein ◽  
B Virus ◽  
Immunofluorescence Studies ◽  
Cellular Partner

ABSTRACT gC1qR, a mitochondrial matrix protein, was identified as the main cellular partner of the hepatitis B virus P22 protein. We demonstrated by immunofluorescence studies that some P22 molecules were colocalized with the endogenous gC1qR in both the cytoplasm and the nucleus but never in the mitochondria. We also showed that the last 34 amino acids of P22 were involved in the association with gC1qR.

scholarly journals The Rift Valley Fever virus protein NSm and putative cellular protein interactions

2012 ◽  
Vol 9 (1) ◽  
pp. 139 ◽  
Author(s):  
Cecilia Engdahl ◽  
Jonas Näslund ◽  
Lena Lindgren ◽  
Clas Ahlm ◽  
Göran Bucht
Keyword(s):  
Protein Interactions ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Cellular Protein ◽  
Fever Virus ◽  
Virus Protein ◽  
Valley Fever

scholarly journals The Chicken Anemia Virus-Derived Protein Apoptin Requires Activation of Caspases for Induction of Apoptosis in Human Tumor Cells

2000 ◽  
Vol 74 (15) ◽  
pp. 7072-7078 ◽  
Author(s):  
A. A. A. M. Danen-van Oorschot ◽  
A. J. van der Eb ◽  
M. H. M. Noteborn
Keyword(s):  
Mammalian Cells ◽  
Caspase 3 ◽  
Human Tumor ◽  
Chemotherapeutic Agents ◽  
Chicken Anemia Virus ◽  
Virus Protein ◽  
Nuclear Morphology ◽  
Induction Of Apoptosis ◽  
Induced Apoptosis ◽  
Anemia Virus

ABSTRACT The chicken anemia virus protein Apoptin has been shown to induce apoptosis in a large number of transformed and tumor cell lines, but not in primary cells. Whereas many other apoptotic stimuli (e.g., many chemotherapeutic agents and radiation) require functional p53 and are inhibited by Bcl-2, Apoptin acts independently of p53, and its activity is enhanced by Bcl-2. Here we study the involvement of caspases, an important component of the apoptotic machinery present in mammalian cells. Using a specific antibody, active caspase-3 was detected in cells expressing Apoptin and undergoing apoptosis. Although Apoptin activity was not affected by CrmA, p35 did inhibit Apoptin-induced apoptosis, as determined by nuclear morphology. Cells expressing both Apoptin and p35 showed only a slight change in nuclear morphology. However, in most of these cells, cytochrome c is still released and the mitochondria are not stained by CMX-Ros, indicating a drop in mitochondrial membrane potential. These results imply that although the final apoptotic events are blocked by p35, parts of the upstream apoptotic pathway that affect mitochondria are already activated by Apoptin. Taken together, these data show that the viral protein Apoptin employs cellular apoptotic factors for induction of apoptosis. Although activation of upstream caspases is not required, activation of caspase-3 and possibly also other downstream caspases is essential for rapid Apoptin-induced apoptosis.

Partial sequence homologies between cytoskeletal proteins, c-myc, Rous sarcoma virus and adenovirus proteins, transducin, and β- and γ-crystallins

1985 ◽  
Vol 5 (2) ◽  
pp. 167-174 ◽  
Author(s):  
M. James ◽  
C. Crabbe
Keyword(s):  
Sequence Homology ◽  
Rous Sarcoma Virus ◽  
Cytoskeletal Proteins ◽  
Partial Sequence ◽  
Virus Protein ◽  
Rous Sarcoma ◽  
Sequence Homologies ◽  
Significant Homology ◽  
Sarcoma Virus ◽  
Simian Sarcoma Virus

Computer based sequence comparisons indicate partial sequence homology between human c-myc, Rous sarcoma virus, adenovirus 7, and simian sarcoma virus proteins and the cytoskeletal proteins desmin, keratin and vimentin. In addition, sections of the oncogene proteins showed partial but significant homology to α and β subunits of transducin, γ-II and β-BP crystallins showed partial but significant homology to the cytoskeletal proteins keratin, vimentin, desmin, α and β-tubulin, and to adenovirus 7 and simian sarcoma virus transforming gene proteins. β-BP crystallin showed partial but significant homology to Rous sarcoma virus protein, and to α and y subunits of transducin. Both crystallins showed partial sequence homology to the GTP-binding protein elongation factor TU from Escherichia coli. These sequence homologies suggest a link between the mechanisms of normal lens cell differentiation, involving modifications to the cytoskeleton and subsequent changes to the pattern of protein synthesis, and mechanisms of neoplastic transformation. Furthermore the transducin-like region on β-crystallin may be important for its interaction with lens membranes and the maintenance of short-range order for lens transparency.

scholarly journals Human Bak induces cell death in Schizosaccharomyces pombe with morphological changes similar to those with apoptosis in mammalian cells.

1997 ◽  
Vol 17 (5) ◽  
pp. 2468-2474 ◽  
Author(s):  
B Ink ◽  
M Zörnig ◽  
B Baum ◽  
N Hajibagheri ◽  
C James ◽  
...  
Keyword(s):  
Cell Death ◽  
Schizosaccharomyces Pombe ◽  
Mammalian Cells ◽  
Morphological Changes ◽  
Yeast Cells ◽  
Bh3 Domain ◽  
Evolutionarily Conserved ◽  
Unicellular Organisms ◽  
Induction Of Apoptosis ◽  
Multicellular Organisms

Apoptosis as a form of programmed cell death (PCD) in multicellular organisms is a well-established genetically controlled process that leads to elimination of unnecessary or damaged cells. Recently, PCD has also been described for unicellular organisms as a process for the socially advantageous regulation of cell survival. The human Bcl-2 family member Bak induces apoptosis in mammalian cells which is counteracted by the Bcl-x(L) protein. We show that Bak also kills the unicellular fission yeast Schizosaccharomyces pombe and that this is inhibited by coexpression of human Bcl-x(L). Moreover, the same critical BH3 domain of Bak that is required for induction of apoptosis in mammalian cells is also required for inducing death in yeast. This suggests that Bak kills mammalian and yeast cells by similar mechanisms. The phenotype of the Bak-induced death in yeast involves condensation and fragmentation of the chromatin as well as dissolution of the nuclear envelope, all of which are features of mammalian apoptosis. These data suggest that the evolutionarily conserved metazoan PCD pathway is also present in unicellular yeast.

scholarly journals Puma, a critical mediator of cell death — one decade on from its discovery

2012 ◽  
Vol 17 (4) ◽  
Author(s):  
Paweł Hikisz ◽  
Zofia Kiliańska
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Membrane ◽  
Viral Infections ◽  
Outer Mitochondrial Membrane ◽  
Caspase Activation ◽  
Bh3 Domain ◽  
Puma Gene ◽  
Induction Of Apoptosis

AbstractPUMA (p53 upregulated modulator of apoptosis) is a pro-apoptotic member of the BH3-only subgroup of the Bcl-2 family. It is a key mediator of p53-dependent and p53-independent apoptosis and was identified 10 years ago. The PUMA gene is mapped to the long arm of chromosome 19, a region that is frequently deleted in a large number of human cancers. PUMA mediates apoptosis thanks to its ability to directly bind known anti-apoptotic members of the Bcl-2 family. It mainly localizes to the mitochondria. The binding of PUMA to the inhibitory members of the Bcl-2 family (Bcl-2-like proteins) via its BH3 domain seems to be a critical regulatory step in the induction of apoptosis. It results in the displacement of the proteins Bax and/or Bak. This is followed by their activation and the formation of pore-like structures on the mitochondrial membrane, which permeabilizes the outer mitochondrial membrane, leading to mitochondrial dysfunction and caspase activation. PUMA is involved in a large number of physiological and pathological processes, including the immune response, cancer, neurodegenerative diseases and bacterial and viral infections.

scholarly journals Spir-1 promotes IRF3 activation and is targetted by vaccinia virus protein K7

2020 ◽  
Author(s):  
Alice Abreu Torres ◽  
Stephanie L. Macilwee ◽  
Amir Rashid ◽  
Sarah E. Cox ◽  
Jonas D. Albarnaz ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Cellular Protein ◽  
Actin Binding ◽  
Virus Protein ◽  
Restriction Factors ◽  
Binding Domains ◽  
Dead Box ◽  
Viral Restriction ◽  
Mouse Cells ◽  
Irf3 Activation

AbstractCharacterisation of viral proteins that mediate immune evasion enables identification of host proteins that function in innate immunity and act as viral restriction factors. This is shown here with vaccinia virus (VACV) protein K7. K7 is a virulence factor that inhibits activation of IRF3 and NF-κB and binds the DEAD-box RNA helicase 3 (DDX3). In this study, Spir-1 is characterised as an additional cellular protein bound by K7 during VACV infection. Spir-1 belongs to a family of actin-binding proteins, however its interaction with K7 does not require its actin-binding domains, suggesting a new function. In human and mouse cells lacking Spir-1, IRF3 activation is impaired, whereas, conversely, Spir-1 overexpression enhanced IRF3 activation. Like DDX3, Spir-1 interacts with K7 directly via a diphenylalanine motif that also is required to promote IRF3 activation. The biological importance of Spir-1 in the response to virus infection is shown by enhanced replication/spreading of VACV in Spir-1 knockout cells. Thus Spir-1 is a new viral restriction factor that functions to enhance IRF3 activation.

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