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41.
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43.
Alpha and lambda interferon together mediate suppression of CD4 T cells induced by respiratory syncytial virus
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Chi B Dickensheets HL Spann KM Alston MA Luongo C Dumoutier L Huang J Renauld JC Kotenko SV Roederer M Beeler JA Donnelly RP Collins PL Rabin RL 《Journal of virology》2006,80(10):5032-5040
The mechanism by which respiratory syncytial virus (RSV) suppresses T-cell proliferation to itself and other antigens is poorly understood. We used monocyte-derived dendritic cells (MDDC) and CD4 T cells and measured [(3)H]thymidine incorporation to determine the factors responsible for RSV-induced T-cell suppression. These two cell types were sufficient for RSV-induced suppression of T-cell proliferation in response to cytomegalovirus or Staphylococcus enterotoxin B. Suppressive activity was transferable with supernatants from RSV-infected MDDC and was not due to transfer of live virus or RSV F (fusion) protein. Supernatants from RSV-infected MDDC, but not MDDC exposed to UV-killed RSV or mock conditions, contained alpha interferon (IFN-alpha; median, 43 pg/ml) and IFN-lambda (approximately 1 to 20 ng/ml). Neutralization of IFN-alpha with monoclonal antibody (MAb) against one of its receptor chains, IFNAR2, or of IFN-lambda with MAb against either of its receptor chains, IFN-lambdaR1 (interleukin 28R [IL-28R]) or IL-10R2, had a modest effect. In contrast, blocking the two receptors together markedly reduced or completely blocked the RSV-induced suppression of CD4 T-cell proliferation. Defining the mechanism of RSV-induced suppression may guide vaccine design and provide insight into previously uncharacterized human T-cell responses and activities of interferons. 相似文献
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45.
Yanshan Zhu Keng Yih Chew Melanie Wu Anjana C. Karawita Georgina McCallum Lauren E. Steele Ayaho Yamamoto Larisa I. Labzin Tejasri Yarlagadda Alexander A. Khromykh Xiaohui Wang Julian D. J. Sng Claudia J. Stocks Yao Xia Tobias R. Kollmann David Martino Merja Joensuu Frdric A. Meunier Giuseppe Balistreri Helle Bielefeldt-Ohmann Asha C. Bowen Anthony Kicic Peter D. Sly Kirsten M. Spann Kirsty R. Short 《PLoS biology》2022,20(8)
Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remain to be determined. Here, we use primary nasal epithelial cells (NECs) from children and adults, differentiated at an air–liquid interface to show that the ancestral SARS-CoV-2 replicates to significantly lower titers in the NECs of children compared to those of adults. This was associated with a heightened antiviral response to SARS-CoV-2 in the NECs of children. Importantly, the Delta variant also replicated to significantly lower titers in the NECs of children. This trend was markedly less pronounced in the case of Omicron. It is also striking to note that, at least in terms of viral RNA, Omicron replicated better in pediatric NECs compared to both Delta and the ancestral virus. Taken together, these data show that the nasal epithelium of children supports lower infection and replication of ancestral SARS-CoV-2, although this may be changing as the virus evolves.Children typically experience more mild symptoms of COVID-19 when compared to adults; why is this? This study uses nasal epithelial cells from children and adults to show that the ancestral SARS-CoV-2 and Delta, but not the Omicron variant, replicate less efficiently in pediatric nasal epithelial cells. 相似文献
46.
Positions of multiple insertions in SSU rDNA of lichen-forming fungi 总被引:11,自引:3,他引:8
Lichen-forming fungi, in symbiotic associations with algae, frequently have
nuclear small subunit ribosomal DNA (SSU rDNA) longer than the 1,800
nucleotides typical for eukaryotes. The lichen-forming ascomycetous fungus
Lecanora dispersa contains insertions at eight distinct positions of its
SSU rDNA; the lichen-forming fungi Calicium tricolor and Porpidia
crustulata each contain one insertion. Insertions are not limited to fungi
that form lichens; the lichen ally Mycocalicium albonigrum also contains
two insertions. Of the 11 insertion positions now reported for
lichen-forming fungi and this ally, 6 positions are known only from
lichen-forming fungi. Including the 4 newly reported in this study,
insertions are now known from at least 17 positions among all reported SSU
rDNA sequences. Insertions, most of which are Group I introns, are reported
in fungal and protistan lineages and occur at corresponding positions in
genomes as phylogenetically distant as the nuclei of fungi, green algae,
and red algae. Many of these positions are exposed in the mature rRNA
tertiary structure and may be subject to independent insertion of introns.
Insertion of introns, accompanied by their sporadic loss, accounts for the
scattered distribution of insertions observed within the SSU rDNA of these
diverse organisms.
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47.
The extent of polylactosamine glycosylation of MDCK LAMP-2 is determined by its Golgi residence time 总被引:2,自引:1,他引:1
The increased polylactosamine glycosylation of LAMP-2 in MDCK cells
cultured for 1 day relative to cells cultured for 3 days has been
correlated with its slower rate of Golgi transit (Nabi and Rodriguez-
Boulan, 1993, Mol. Biol. Cell., 4, 627-635). To determine if the
differential polylactosamine glycosylation of LAMP-2 is a consequence of
glycosyltransferase expression levels, the activities of beta1- 6GlcNAc-TV,
beta1-3GlcNAc-T(i), beta1-2GlcNAc-TI, beta1, 4Gal-T, alpha2- 6sialyl-T, and
alpha2-3sialyl-T were assayed and no significant differences in the
activities of these enzymes in 1 and 3 day cell extracts were detected.
During MDCK epithelial polarization, the Golgi apparatus undergoes
morphological changes and apiconuclear Golgi networks were more evident in
3 day cells. Treatment with nocodazole disrupted Golgi networks and
generated numerous Golgi clusters in both 1 day and 3 day cells. In the
presence of nocodazole the differential migration of LAMP-2 in 1 and 3 day
MDCK cells was maintained and could be eliminated by treatment with
endo-beta-galactosidase, indicating that gross Golgi morphology did not
influence the extent of LAMP-2 polylactosamine glycosylation. Nocodazole
treatment did, however, result in the faster migration of LAMP-2 which was
not due to modification of core N-glycans as the precursor form of the
glycoprotein migrated with an identical molecular size. Following
incubation at 20 degrees C, which prevents the exit of proteins from the
trans-Golgi network, the molecular size of LAMP-2 increased to a similar
extent in both 1 and 3 day MDCK cells. Extending the time of incubation at
20 degrees C did not influence the size of LAMP-2, demonstrating that its
glycosylation is modified not by its retention within the Golgi but rather
by its equivalent slower Golgi passage at the lower temperature in both 1
and 3 day cells. An identical effect was observed in nocodazole treated
cells, demonstrating that Golgi residence time determines the extent of
LAMP-2 polylactosamine glycosylation, even in isolated Golgi clusters.
相似文献
48.
Incorporation of axonally transported glycoproteins into axolemma during nerve regeneration 总被引:14,自引:4,他引:10
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The insertion of axonally transported fucosyl glycoproteins into the axolemma of regenerating nerve sprouts was examined in rat sciatic motor axons at intervals after nerve crush. [(3)H]Fucose was injected into the lumbar ventral horns and the nerves were removed at intervals between 1 and 14 d after labeling. To follow the fate of the “pulse- labeled” glycoproteins, we examined the nerves by correlative radiometric and EM radioautographic approaches. The results showed, first, that rapidly transported [(3)H]fucosyl glycoproteins were inserted into the axolemma of regenerating sprouts as well as parent axons. At 1 d after delivery, in addition to the substantial mobile fraction of radioactivity still undergoing bidirectional transport within the axon, a fraction of label was already associated with the axolemma. Insertion of labeled glycoproteins into the sprout axolemma appeared to occur all along the length of the regenerating sprouts, not just in sprout terminals. Once inserted, labeled glycoproteins did not undergo extensive redistribution, nor did they appear in sprout regions that formed (as a result of continued outgrowth) after their insertion. The amount of radioactivity in the regenerating nerves decreased with time, in part as a result of removal of transported label by retrograde transport. By 7-14 d after labeling, radioautography showed that almost all the remaining radioactivity was associated with axolemma. The regenerating sprouts retained increased amounts of labeled glycoproteins; 7 or 14 d after labeling, the regenerating sprouts had over twice as much of radioactivity as comparable lengths of control nerves or parent axons. One role of fast axonal transport in nerve regeneration is the contribution to the regenerating sprout of glycoproteins inserted into the axolemma; these membrane elements are added both during longitudinal outgrowth and during lateral growth and maturation of the sprout. 相似文献
49.
JW Mills ADC MacKnight JA Jarrell JM Dayer DA Ausiello 《The Journal of cell biology》1981,88(3):637-643
To determine the specificity and efficacy of [(3)H]ouabain binding as a quantitative measure of the Na(+) pump (Na(+), K(+)-ATPase) and as a marker for the localization of pumps involved in transepithelial Na(+)-transport, we analyzed the interaction of [(3)H]ouabain with its receptor in pig kidney epithelial (LLC-PK(1)) cells. When these epithelial cells are depleted of Na(+) and exposed to 2 muM [(3)H]ouabain in a Na(+)-free medium, binding is reduced by 90 percent. When depleted of K(+) and incubated in a K(+)- free medium, the ouabain binding rate is increase compared with that measured at 5 mM. This increase is only demonstable when Na(+) is present. The increased rate could be attributed to the predominance of the Na(+)-stimulated phosphorylated form of the pump, as K(+) is not readily available to stimulate dephosphorylation. However, some binding in the K(+)-free medium is attributable to pump turnover (and therefore, recycling of K(+)), because analysis of K(+)-washout kinetics demonstrated that addition of 2 muM ouabain to K(+)-depleted cells increased the rate of K(+) loss. These results indicate that in intact epithelial cells, unlike isolated membrane preparations, the most favorable condition for supporting ouabain binding occurs when the Na(+), K(+)-ATPase is operating in the Na(+)-pump mode or is phosphorylated in the presence of Na(+). When LLC-PK(1) cells were exposed to ouabain at 4 degrees C, binding was reduced by 97 percent. Upon rewarming, the rate of binding was greater than that obtained on cells kept at a constant 37 degrees C. However, even at this accelerated rate, the time to reach equilibrium was beyond what is required for cells, swollen by exposure to cold, to recover normal volume. Thus, results from studies that have attempted to use ouabain to eliminate the contribution of the conventional Na(+) pump to volume recovery must be reevaluated if the exposure to ouabain was done in the cold or under conditions in which the Na(+) pump is not operating. 相似文献
50.