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1.
Protein Kinase PKR Mediates the Apoptosis Induction and Growth Restriction Phenotypes of C Protein-Deficient Measles Virus 总被引:1,自引:0,他引:1 下载免费PDF全文
Ann M. Toth Patricia Devaux Roberto Cattaneo Charles E. Samuel 《Journal of virology》2009,83(2):961-968
The measles virus (MV) accessory proteins V and C play important roles in MV replication and pathogenesis. Infection with recombinant MV lacking either V or C causes more cell death than infection with the parental vaccine-equivalent virus (MVvac), and C-deficient virus grows poorly relative to the parental virus. Here, we show that a major effector of the C phenotype is the RNA-dependent protein kinase PKR. Using human HeLa cells stably deficient in PKR as a result of RNA interference-mediated knockdown (PKRkd cells), we demonstrated that a reduction in PKR partially rescued the growth defect of C knockout (Cko) virus but had no effect on the growth of either wild-type (WT) or V knockout (Vko) virus. Increased growth of the Cko virus in PKRkd cells correlated with increased viral protein expression, while defective growth and decreased protein expression in PKR-sufficient cells correlated with increased phosphorylation of PKR and the α subunit of eukaryotic initiation factor 2. Furthermore, infection with WT, Vko, or especially Cko virus caused significantly less apoptosis in PKRkd cells than in PKR-sufficient cells. Although apoptosis induced by Cko virus infection in PKR-sufficient cells was blocked by a caspase antagonist, the growth of Cko virus was not restored to the WT level by treatment with this pharmacologic inhibitor. Taken together, these results indicate that PKR plays an important antiviral role during MV infection but that the virus growth restriction by PKR is not dependent upon the induction of apoptosis. Furthermore, the results establish that a principal function of the MV C protein is to antagonize the proapoptotic and antiviral activities of PKR. 相似文献
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Myelography using pantopaque in greater than usual amount with a variation in technique, which is described, is believed to provide increased accuracy in differential diagnosis and precise localization of lesions in the lumbar spine. The need for multiple space exploration is eliminated and more detailed information concerning the size and shape of lesions is provided as compared to that secured by the use of 3 or 6 cc. of opaque medium and fluoroscopic examination alone. In 53 cases in which lumbar myelography was performed and the diagnosis verified or disproved at operation, there was a 5 per cent diagnostic error in 41 instances in which the method outlined was used, as compared with 17 per cent error in 12 cases in which only 3 or 6 cc. of radiopaque material and fluoroscopy alone were used. The accuracy of the procedure would appear to warrant its use in the evaluation of patients suspected of having abnormalities of the lumbar discs associated with nerve root compression. 相似文献
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J M Katz W G Laver D O White E M Anders 《Journal of immunology (Baltimore, Md. : 1950)》1985,134(1):616-622
The recognition of influenza virus hemagglutinin (HA) by T lymphocytes was examined by assaying the T cell proliferative response of influenza virus-primed T cells to purified HA of different influenza A subtypes or to isolated heavy (HA1) or light (HA2) polypeptide chains of the HA molecule. The proliferative response to HA was dependent on the activation of an Ly-1+2- subset of T cells and required the presence of nylon wool-adherent, radiation-resistant accessory cells. T cells from mice primed by infection with one strain of type A influenza virus cross-reacted with other purified HA not only of the same subtype as the priming virus but also of serologically distinct subtypes of influenza A (but not B) virus. The response of virus-primed T cells to the homologous HA or to HA of the same subtype was shown to involve recognition of determinants on both the HA1 and the HA2 chains. The recognition of HA of different subtype by cross-reactive T cells appeared to be directed predominantly to determinants on HA2. Because the antibody response to influenza virus HA is not cross-reactive between subtypes and is directed predominantly to determinants on HA1, the present results indicate that at least some of the determinants on HA recognized by T cells are different from those recognized by B cells and that the HA2 chain may be involved primarily in stimulation of T cell rather than B cell immunity. 相似文献
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Charles L. Nunn Peter H. Thrall Kelly Stewart Alexander H. Harcourt 《Evolutionary ecology》2008,22(4):519-543
Emerging infectious diseases threaten a wide diversity of animals, and important questions remain concerning disease emergence
in socially structured populations. We developed a spatially explicit simulation model to investigate whether—and under what
conditions—disease-related mortality can impact rates of pathogen spread in populations of polygynous groups. Specifically,
we investigated whether pathogen-mediated dispersal (PMD) can occur when females disperse after the resident male dies from
disease, thus carrying infections to new groups. We also examined the effects of incubation period and virulence, host mortality
and rates of background dispersal, and we used the model to investigate the spread of the virus responsible for Ebola hemorrhagic
fever, which currently is devastating African ape populations. Output was analyzed using regression trees, which enable exploration
of hierarchical and non-linear relationships. Analyses revealed that the incidence of disease in single-male (polygynous)
groups was significantly greater for those groups containing an average of more than six females, while the total number of
infected hosts in the population was most sensitive to the number of females per group. Thus, as expected, PMD occurs in polygynous
groups and its effects increase as harem size (the number of females) increases. Simulation output further indicated that
population-level effects of Ebola are likely to differ among multi-male–multi-female chimpanzees and polygynous gorillas,
with larger overall numbers of chimpanzees infected, but more gorilla groups becoming infected due to increased dispersal
when the resident male dies. Collectively, our results highlight the importance of social system on the spread of disease
in wild mammals. 相似文献