Inhibitory effect of favipiravir on canine distemper virus replication in vitro / 军事医学

Objective To investigate the inhibitory effect of favipiravir (T-705) on canine distemper virus (CDV) replication in Vero cells and DH82 cells.Methods The growth curves of CDV-11 strains from canine and CDV-3 strains from mink in Vero cells and DH82 cells were determined with indirect immunofluorescence assay and 50％ endpoint titration.The viability of Vero and DH82 cells was determined using the Cell Counting Kit-8.CDV inhibition at different concentrations of T-705 at different time points was measured .Results Cytotoxicity data showed that there was a moderate decline of viability in Vero cells after T-705 treatment, but no apparent cytotoxicity in DH 82 cells.T-705 significantly inhibited the replication of CDV-3 and CDV-11 in both Vero cells and DH82 cells in the test range of 2.441-1250 μg/ml. T-705 exhibited effective and stable antiviral activity when given at different time points post virus challenge .Conclusion Our results demonstrate that T-705 has effective antiviral activity and may be a promising anti-CDV drug candidate .

Contribution of 3CD Region to the Virulence of Enterovirus 71 / 生物医学与环境科学（英文）

Enterovirus 71 is a neuroinvasive virus that is associated with severe neurological complications. We had earlier suggested that the replication capacity of a severe strain was higher than that of a mild strain. The recombinant 3CRV and 3CDRV virus strains were successfully rescued in our previous study. In the present study, we found no difference in virulence between 3CRV and severe strains. However, the capacity of replication and to cause cell injury of 3CDRV strain decreased in vitro, especially at 39.5 °C. Replacement of 3CD region in the severe strain led to milder symptoms, less body weight loss, and lower viral load in ICR mice. Histopathological findings indicated less severe injury in mice infected with 3CDRV strain. This study suggests that the 3CD region contributes to the attenuation of the severe strain, including its replication capacity and temperature sensitivity.

Effects of HIV-1 tat on secretion of TNF-α and IL-1β by U87 cells in AIDS patients with or without AIDS dementia complex / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To explore the role of HIV-1 tat gene variations in AIDS dementia complex (ADC) pathogenesis.</p><p><b>METHODS</b>HIV-1 tat genes derived from peripheral spleen and central basal ganglia of an AIDS patient with ADC and an AIDS patient without ADC were cloned for sequence analysis. HIV-1 tat gene sequence alignment was performed by using CLUSTAL W and the phylogentic analysis was conducted by using Neighbor-joining with MEGA4 software. All tat genes were used to construct recombinant retroviral expressing vector MSCV-IRES-GFP/tat. The MSCV-IRES-GFP/tat was cotransfected into 293T cells with pCMV-VSV-G and pUMVC vectors to assemble the recombinant retrovirus. After infection of gliomas U87 cells with equal amount of the recombinant retrovirus, TNF-α, and IL-1β concentrations in the supernatant of U87 cells were determined with ELISA.</p><p><b>RESULTS</b>HIV-1 tat genes derived from peripheral spleen and central basal ganglia of the AIDS patient with ADC and the other one without ADC exhibited genetic variations. Tat variations and amino acid mutation sites existed mainly at Tat protein core functional area (38-47aa). All Tat proteins could induce U87 cells to produce TNF-α and IL-1β, but the level of IL-1β production was different among Tat proteins derived from the ADC patient's spleen, basal ganglia, and the non-ADC patient's spleen. The level of Tat proteins derived from the ADC patient's spleen, basal ganglia, and the non-ADC patient's spleen were obviously higher than that from the non-ADC patient's basal ganglia.</p><p><b>CONCLUSION</b>Tat protein core functional area (38-47aa) may serve as the key area of enhancing the secretion of IL-1β. This may be related with the neurotoxicity of HIV-1 Tat.</p>