RESUMO
Simian varicella virus (SVV) is closely related to varicella-zoster virus (VZV), the causative agent of chickenpox and shingles. The SVV and VZV gene 61 polypeptides are homologs of the HSV-1 ICP0, a viral transactivator which appears to play a role in viral latency and reactivation. In this study, the molecular properties of the SVV 61 were characterized. The SVV open reading frame (ORF) 61 encodes a 54.1-kDa polypeptide with 37% amino acid identity to the VZV 61. Homology to the HSV-1 ICP-0 is limited to a conserved RING finger motif at the amino terminus of the protein. A nuclear localization sequence (nls) at the carboxy-terminus directs the SVV 61 to the cell nucleus, while a SVV 61nls(-) mutant is confined to the cell cytoplasm. The SVV 61 transactivates its own promoter as well as SVV immediate early (IE, ORF 62), early (ORFs 28 and 29), and late (ORF 68) gene promoters in transfected Vero cells. The RING finger and nls motifs are required for efficient SVV 61 transactivation. The SVV 61 has no effect on the ability of the major SVV transactivator (IE62) to induce SVV promoters. Generation and propagation of a SVV gene 61 deletion mutant demonstrated that the SVV 61 is non-essential for in vitro replication. SVV gene 61 is expressed in liver, lung, and neural ganglia of infected monkeys during acute simian varicella.
Assuntos
Genes Virais , Transativadores/genética , Varicellovirus/genética , Replicação Viral/fisiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Chlorocebus aethiops , DNA Viral/genética , DNA Viral/isolamento & purificação , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/virologia , Herpesvirus Humano 3/genética , Humanos , Rim , Dados de Sequência Molecular , Fases de Leitura Aberta , Doenças dos Primatas/virologia , Primatas , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Varicellovirus/fisiologia , Células VeroRESUMO
An open-label dose-escalation trial was performed to assess the safety and tolerability of high doses of coenzyme Q10 (CoQ10) in ALS. CoQ10, a cofactor in mitochondrial electron transfer, may improve the mitochondrial dysfunction in ALS. In this study, CoQ10 was safe and well tolerated in 31 subjects treated with doses as high as 3,000 mg/day for 8 months.
Assuntos
Esclerose Lateral Amiotrófica/tratamento farmacológico , Sistema Nervoso Central/efeitos dos fármacos , Degeneração Neural/prevenção & controle , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Ubiquinona/análogos & derivados , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/fisiopatologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/fisiopatologia , Coenzimas , Relação Dose-Resposta a Droga , Tolerância a Medicamentos/fisiologia , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Feminino , Sequestradores de Radicais Livres/administração & dosagem , Sequestradores de Radicais Livres/efeitos adversos , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Degeneração Neural/tratamento farmacológico , Degeneração Neural/metabolismo , Neurônios/metabolismo , Fármacos Neuroprotetores/efeitos adversos , Fármacos Neuroprotetores/sangue , Ubiquinona/administração & dosagem , Ubiquinona/efeitos adversos , Ubiquinona/sangueRESUMO
Simian varicella is used as a model to investigate varicella-zoster virus pathogenesis and to evaluate antiviral therapies. In this study, the simian varicella virus (SVV) glycoprotein L (gL) was characterized along with its association with glycoprotein H (gH). The SVV gL gene encodes a predicted 175 amino acid polypeptide that shares 43.5% and 27.9% amino acid identity with the VZV gL and HSV-1 gL, respectively. The SVV gL polypeptide sequence lacks a consensus glycosylation site and a typical signal sequence, but does possess an endoplasmic reticulum targeting sequence found commonly in chaperone proteins. Transcriptional analysis indicated that the SVV gL and the uracil DNA glycosylase (UDG) genes share a common 5' RNA start site and are co-expressed on a 2.0 kb transcript. gL and gH expression in SVV-infected Vero cells was demonstrated by immunofluorescence and immunoprecipitation analyses using specific antisera generated against gL and gH peptides. Similar to other herpesvirus gH and gL homologs, the SVV gL and gH form a complex within infected cells. gL and gH transcripts and antigens were detected in tissues of monkeys with acute simian varicella. The simian varicella model offers an opportunity to investigate the role of the gL and gH in viral pathogenesis.
Assuntos
Varicellovirus/fisiologia , Proteínas do Envelope Viral/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Varicela/virologia , Chlorocebus aethiops , Infecções por Herpesviridae/virologia , Dados de Sequência Molecular , Análise de Sequência de DNA , Varicellovirus/patogenicidade , Células Vero , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genéticaRESUMO
Simian varicella virus (SVV) infection of non-human primates is used as a model to study the pathogenesis and latency of varicella-zoster virus (VZV), the etiological agent of chickenpox and shingles. Uracil DNA glycosylase (UDG) is a DNA repair enzyme responsible for excision of uracil residues misincorporated into DNA. UDG is conserved throughout the herpesvirus family and may play an important role in viral pathogenesis. This study identified a 300 amino acid SVV UDG that shares 53.9% amino acid identity with the VZV UDG. The SVV UDG is expressed in infected Vero cells as determined by reverse transcriptase polymerase chain reaction (RT-PCR) and Northern blot analysis. The SVV UDG is encoded on a 2.0 kb transcript which also appears to encode the SVV glycoprotein L (gL) and the VZV gene 58 homolog. The SVV UDG is enzymatically active as determined by the ability of a SVV UDG-maltose binding protein fusion construct to remove [(3)H]-uracil incorporated into DNA.
