ABSTRACT
Foamy viruses belong to the Spumaretrovirinae subfamily member of the Retroviridae family and produce nonpathogenic infection to hosts in the natural conditions. However, infections of foamy viruses can dramatically cause severe cytopathic effects in vitro. To date, the exact molecular mechanism has remained unclear which implied the tremendous importance of virus-host cell immune reactions. In this study, we found that the transactivator Tas in two foamy viruses isolated from Old World Monkey (OWM) induced obvious inhibition of cell proliferation via the upregulation of Foxo3a expression. It was mediated by the generation of ROS and the initiation of ER stress, and ultimately, the mitochondrial apoptosis pathway was triggered. Notably, PFV Tas contributed to the accumulation of G0/G1 phase cycle arrest induced by the activation of the p53 signaling pathway and the nuclear transportation of HDAC4 via upregulating PPM1E expression. Together, these results demonstrated the different survival strategies by which foamy virus can hijack host cell cytokines and regulate virus-host cell interactions.
Subject(s)
Spumavirus , Apoptosis , Cell Cycle Checkpoints , Cell Line , Cell Proliferation , Host Microbial Interactions , Spumavirus/genetics , Spumavirus/metabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinical efficacy and safety of intravenous injection of low-dose versus high-dose gamma globulin combined with glucocorticoid pulse therapy in the treatment of children with moderate/severe acute Guillain-Barré syndrome (GBS).</p><p><b>METHODS</b>A total of 100 children with moderate/severe acute GBS were randomly assigned to low-dose group (n=48) and high-dose group (n=52). The children in the low-dose and high-dose groups were treated with 0.2 g/(kg · d) and 0.4 g/(kg · d) gamma globulin respectively combined with methylprednisolone. The two groups were compared in terms of the time to improvements of symptoms after treatment, serum levels of inflammatory factors, proportion of children undergoing invasive ventilation, treatment response rate, and adverse events.</p><p><b>RESULTS</b>After 5 days of treatment, the low- and high-dose groups had significant reductions in serum levels of tumor necrosis factor-α, interleukin-6, and C-reactive protein, and there were no significant differences in the reductions of these markers between the two groups. There were no significant differences between the two groups in the time to recovery of respiratory muscle paralysis, time to an improvement in muscle strength of one grade, time to recovery of sensory disturbance, and length of hospital stay. There was no significant difference in the treatment response rate between the low- and high-dose groups (90% vs 92%). There were also no significant differences in the incidence rates of pyrexia, headache, nausea, and palpitation between the two groups.</p><p><b>CONCLUSIONS</b>Low-dose versus high-dose gamma globulin combined with methylprednisolone pulse therapy have comparable clinical efficacy and safety in the treatment of children with moderate/severe acute GBS.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , C-Reactive Protein , Guillain-Barre Syndrome , Drug Therapy , Length of Stay , Methylprednisolone , Tumor Necrosis Factor-alpha , Blood , gamma-GlobulinsABSTRACT
The recombined adenovirus DNA was transfected into 293 cells for packing and amplification of replication-deficient Ad-CMV-E6/E7, Ad-K14 -E6/E7 virus was purified by CsCl density gradient centrifugation , recombined adenovirus Ad-CMV-E6/E7, Ad-K14 -E6/E7 were used as experimental group, while pAd-CMV and pAdtrack-K14 were used as control group. Four of them were injected through one main vein of nude mice tail respectively. These mice were then treated with 0.05 mg 17beta-estradiol over 12 weeks. Mice were anaesthesiaed with 2.5% Avertint and the vagina, mammary gland, ovaries and uterus were dissected and fixed in 3.75% paraformaldehyde overnight at 4 degrees C. Paraffin-embedded sections, HE staining and identification of P53 and Bcl-2 protein via immunohistochemistry were performed. The expression of E6/E7 was verified by RT-PCR in different tissue of nude mice. HE staining showed evident hyperplasy in cervix-uterus transformation zone of experimental group 2. The expression of mutant P53 and Bcl-2 were higher than control group via immunohistochemical S-P method in uterus stroma-cell. Western blotting also showed that E6 protein was expressed. The expression of E6/E7 was higher than control group by human cytokeratin promoter 14 and hyperlasy changes were detected in epithelial tissue of cervix-uterus transformation zone.
Subject(s)
Animals , Female , Humans , Mice , Adenoviridae , Genetics , Blotting, Western , Cell Line , Genital Diseases, Female , Pathology , Virology , Genitalia, Female , Pathology , Virology , Immunohistochemistry , Mammary Glands, Animal , Metabolism , Pathology , Mice, Nude , Oncogene Proteins, Viral , Genetics , Metabolism , Ovary , Metabolism , Pathology , Papillomaviridae , Metabolism , Physiology , Papillomavirus E7 Proteins , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Repressor Proteins , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Suppressor Protein p53 , Metabolism , Uterus , Metabolism , Pathology , Vagina , Metabolism , PathologyABSTRACT
Argyrogramma agnata has been selected as a substitutive host insect for producing Dendrolimus punctatus Cytoplasmic Polyhedrosis Virus (DpCPV). In our experiment, it is very susceptible to DpCPV. The DpCPV produced in A. agnata is designated Aa-DpCPV. The cytoplasmic polyhedra body (CPB), the virion size and the shape of Aa-DpCPV are same as that of its original DpCPV (DpCPV-W1984). The RNA bands of Aa-DpCPV and DpCPV-W1984 all have 10 RNA segments respectively in 3% PAGE, which molecular weights ranged in size from 2.98×106 to 0.66×106 Dalton. Aa-DpCPV has the same strong toxicity as that of DpCPV-W1984 (from D. punctatus) to D. punctatus (Walker) larva. So it can be applied to the pine caterpillar control. The DpCPV yield in A.agnata is 2.5×108CPB/larva.
