Biomedical subjects

Jason A Aligo

Publications and source records attributed to Jason A Aligo.

3 recordsLinked to original sources

PubMed2005

The role of simian virus 5 V protein on viral RNA synthesis.

The paramyxovirus simian virus 5 (SV5) has seven genes but encodes eight known viral proteins. The V/P gene is transcribed into two mRNA species: V mRNA from a faithful transcription of the gene and P mRNA from transcription with addition of two G residues at a specific site of the gene. V, a 222-amino acid (AA) residue protein, and P, a 392 AA residue protein, share an identical N-terminus domain of 164 amino acid residues. P is essential for SV5 RNA replication and transcription. Whereas it is known that V plays important roles in virus pathogenesis, the role of V in SV5 replication and transcription is not clear. A mini-genome system, free of vaccinia virus gene expression system, consisting of plasmids expressing NP, P, and L, as well as a plasmid encoding a reporter gene, chloramphenicol acetyltransferase (CAT) flanked by SV5 trailer and leader sequences under control of a bacteriophage T7 RNA polymerase promoter, has been established to examine the role of V in SV5 RNA transcription and replication. Addition of V-expressing plasmid in the mini-genome system caused inhibition of the reporter gene expression, suggesting that V plays a role in regulating SV5 gene expression. By examining the amount of encapsidated viral RNA genome using reverse transcription with primer annealing to viral anti-genome RNA and PCR, it was found that expression of V reduced the amount of viral RNA genome in the mini-genome system, suggesting that V inhibits viral RNA replication. To examine whether the V protein inhibits viral RNA transcription as well, a mini-genome system with a defective anti-genome promoter (AGP) such that a reporter gene (luciferase, Luc) expression is only derived from transcription of newly produced mini-genome and not from de novo replicated viral genome due to the defect in replication element has been utilized. The V protein inhibited luciferase expression from the mini-genome with a defective AGP, suggesting V inhibits SV5 transcription. Thus, SV5 V inhibits both SV5 RNA replication and transcription.

Animals↗

PubMed2005

Solution and solid-state variation of cupric phenanthroline complexes.

The 1:1 cupric-phenanthroline complexes, [Cu(5,6-Me2-phen)(MeCN)2(BF4)](BF4) (1), [Cu(o-phen)(MeCN)2(H2O)](BF4)2 (2), and [Cu(5-Cl-phen)(MeCN)2(BF4)](BF4) (3), have been prepared and characterized by X-ray crystallography. The structures of 1 and 3 are characterized by an equatorial plane about the copper center consisting of a phenanthroline ligand and two acetonitrile ligands. The copper units are connected by bridging counterions in the axial positions of the pseudo-octahedral metal centers to form one-dimensional solid-state linkages. The structure of 2 contains the same equatorial plane as 1 and 3, but an axial water ligand completes a square pyramidal geometry for each discrete metal unit. Although the solid-state structures vary for the three complexes, characterization through electronic spectroscopy and cyclic voltammetry reveals similar behavior for all three complexes in solution.

Journal Article↗

PubMed2004

Conserved cysteine-rich domain of paramyxovirus simian virus 5 V protein plays an important role in blocking apoptosis.

The paramyxovirus family includes many well-known human and animal pathogens as well as emerging viruses such as Hendra virus and Nipah virus. The V protein of simian virus 5 (SV5), a prototype of the paramyxoviruses, contains a cysteine-rich C-terminal domain which is conserved among all paramyxovirus V proteins. The V protein can block both interferon (IFN) signaling by causing degradation of STAT1 and IFN production by blocking IRF-3 nuclear import. Previously, it was reported that recombinant SV5 lacking the C terminus of the V protein (rSV5VDeltaC) induces a severe cytopathic effect (CPE) in tissue culture whereas wild-type (wt) SV5 infection does not induce CPE. In this study, the nature of the CPE and the mechanism of the induction of CPE were investigated. Through the use of DNA fragmentation, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling, and propidium iodide staining assays, it was shown that rSV5VDeltaC induced apoptosis. Expression of wt V protein prevented apoptosis induced by rSV5VDeltaC, suggesting that the V protein has an antiapoptotic function. Interestingly, rSV5VDeltaC induced apoptosis in U3A cells (a STAT1-deficient cell line) and in the presence of neutralizing antibody against IFN, suggesting that the induction of apoptosis by rSV5VDeltaC was independent of IFN and IFN-signaling pathways. Apoptosis induced by rSV5VDeltaC was blocked by a general caspase inhibitor, Z-VAD-FMK, but not by specific inhibitors against caspases 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 13, suggesting that rSV5VDeltaC-induced apoptosis can occur in a caspase 12-dependent manner. Endoplasmic reticulum stress can lead to activation of caspase 12; compared to the results seen with mock and wt SV5 infection, rSV5VDeltaC infection induced ER stress, as demonstrated by increased expression levels of known ER stress indicators GRP 78, GRP 94, and GADD153. These data suggest that rSV5VDeltaC can trigger cell death by inducing ER stress.

Animals↗