Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The twin challenges of immunodominance and heterologous immunity have hampered discovery of an effective vaccine against all four dengue viruses. Here, we explore how the T cell competition and selection underlying these asymmetrical properties impede effective T cell vaccine design. The theory we develop predicts dengue vaccine clinical trial data well. From the insights that we gain by this theory, we propose two new ideas for design of epitope-based T cell vaccines against dengue: polytopic injection and subdominant epitope priming.
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PMID:Sculpting the immunological response to dengue fever by polytopic vaccination. 1641 56

Flaviviruses assemble as fusion-incompetent immature particles and subsequently undergo conformational change leading to release of infectious virions. Flavivirus infections also produce combined 'mosaic' particles. Here, using cryo-electron tomography, we report that mosaic particles of dengue virus type 2 had glycoproteins organized into two regions of mature and immature structure. Furthermore, particles of a maturation-deficient mutant had their glycoproteins organized into two regions of immature structure with mismatching icosahedral symmetries. It is therefore apparent that the maturation-related reorganization of the flavivirus glycoproteins is not synchronized across the whole virion, but is initiated from one or more nucleation centres. Similar deviation from icosahedral symmetry might be relevant to the asymmetrical mode of genome packaging and cell entry of other viruses.
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PMID:Maturation of flaviviruses starts from one or more icosahedrally independent nucleation centres. 2156 48