Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Viral matrix proteins of several enveloped RNA viruses play important roles in virus assembly and budding and are by themselves able to bud from the cell surface in the form of lipid-enveloped, virus-like particles (VLPs). Three motifs (PT/SAP, PPxY, and YxxL) have been identified as late budding domains (L-domains) responsible for efficient budding. L-domains can functionally interact with cellular proteins involved in vacuolar sorting (VPS4A and TSG101) and endocytic pathways (Nedd4), suggesting involvement of these pathways in virus budding. Ebola virus VP40 has overlapping PTAP and PPEY motifs, which can functionally interact with TSG101 and Nedd4, respectively. As for vesicular stomatitis virus (VSV), a PPPY motif within M protein can interact with Nedd4. In addition, M protein has a PSAP sequence downstream of the PPPY motif, but the function of PSAP in budding is not clear. In this study, we compared L-domain functions between Ebola virus and VSV by constructing a chimeric M protein (M40), in which the PPPY motif of VSV M is replaced by the L domains of VP40. The budding efficiency of M40 was 10-fold higher than that of wild-type (wt) M protein. Overexpression of a dominant negative mutant of VPS4A or depletion of cellular TSG101 reduced the budding of only M40-containing VLPs but not that of wt M VLPs or live VSV. These findings suggest that the PSAP motif of M protein is not critical for budding and that there are fundamental differences between PTAP-containing viruses (Ebola virus and human immunodeficiency virus type 1) and PPPY-containing viruses (VSV and rabies virus) regarding their dependence on specific host factors for efficient budding.
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PMID:Budding of PPxY-containing rhabdoviruses is not dependent on host proteins TGS101 and VPS4A. 1499 Jun 85

VLPs (virus-like particles) are promising delivery vectors for molecular therapy, since they combine the major advantages of viral vectors with significantly fewer viral vector disadvantages. The present paper describes the molecular construction of chimaeric VLPs based on minimal SIV (simian immunodeficiency virus) and HIV1 components. A chimaeric protein was constructed by fusion of SIV matrix protein (p17) and HIV1 p6 protein, and we demonstrated that the chimaeric proteins assemble as 80 nm nanoparticles containing approximately 7700 chimaeric protein units. Chimaeric VLPs are released from HEK-293T cells (human embryonic kidney cells expressing the large T-antigen of simian virus 40) and are fully encapsulated with lipid membrane. Chimaeric VLPs are produced at 3.7-fold higher levels when compared with SIV p17 VLPs owing to duplication of a PTAP (Pro-Thr-Ala-Pro) domain previously shown as essential for virus particle release. The chimaeric VLPs constructed in the present paper were efficiently pseudotyped with vesicular-stomatitis-virus glycoprotein, as shown by immunoprecipitation assays.
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PMID:Molecular construction of bionanoparticles: chimaeric SIV p17-HIV I p6 nanoparticles with minimal viral protein content. 1739 Nov 1

Self-propagating, infectious, virus-like vesicles (VLVs) are generated when an alphavirus RNA replicon expresses the vesicular stomatitis virus glycoprotein (VSV G) as the only structural protein. The mechanism that generates these VLVs lacking a capsid protein has remained a mystery for over 20 years. We present evidence that VLVs arise from membrane-enveloped RNA replication factories (spherules) containing VSV G protein that are largely trapped on the cell surface. After extensive passaging, VLVs evolve to grow to high titers through acquisition of multiple point mutations in their nonstructural replicase proteins. We reconstituted these mutations into a plasmid-based system from which high-titer VLVs can be recovered. One of these mutations generates a late domain motif (PTAP) that is critical for high-titer VLV production. We propose a model in which the VLVs have evolved in vitro to exploit a cellular budding pathway that is hijacked by many enveloped viruses, allowing them to bud efficiently from the cell surface. Our results suggest a basic mechanism of propagation that may have been used by primitive RNA viruses lacking capsid proteins. Capsids may have evolved later to allow more efficient packaging of RNA, greater virus stability, and evasion of innate immunity.
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PMID:In vitro evolution of high-titer, virus-like vesicles containing a single structural protein. 2538 8