| VP40 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 VP40 matrix protein hexamer, Ebola virus | |||||||||
| Identifiers | |||||||||
| Symbol | VP40 | ||||||||
| Pfam | PF07447 | ||||||||
| InterPro | IPR008986 | ||||||||
| SCOP2 | 1h2c /SCOPe /SUPFAM | ||||||||
| |||||||||
In molecular biology,VP40 is the name of aviral matrix protein. Most commonly, it is found in theEbola virus (EBOV),[1] a type of non-segmented, negative-strandRNAvirus. Ebola virus causes a severe and often fatalhaemorrhagic fever inhumans, known asEbola virus disease. The virus matrixprotein VP40 is a majorstructural protein that plays a central role in virus assembly andbudding at theplasma membrane of infectedcells. VP40proteins work by associating withcellular membranes,interacting with thecytoplasmic tails of glycoproteins andbinding to theribonucleoproteincomplex.[citation needed]
The VP40monomer consists of twoprotein domains, theN-terminal oligomerization domain and theC-terminal membrane-binding domain, connected by a flexible linker. Both the N- and C-terminaldomainsfold intobeta sandwichstructures of similar topology.[2] Within the N-terminal domain are two overlapping L-domains with thesequences PTAP and PPEY atresidues 7 to 13, which are required for efficient budding.[3] L-domains are thought to mediate their function in budding through their interaction with specific host cellular proteins, such asTSG101 and vps-4.[4]
VP40 coordinates numerous functions in the viral life cycle of theEbola virus. These include: regulation of viraltranscription,morphogenesis, packaging and budding of mature virions.[5]
VP40 goes through intermediate states of assembly (e.g. octamers). It has been noted that proteins encoded by EBOV (VP30, VP35, and VP40) act independently as suppressors ofRNA silencing, indicating that the virus actively resists cellular RNAi during replication.[5]
Study of the matrix protein VP40 is important due to the highmortality rate of the Ebola virus, which is listed as aWHO Risk Group 4 Pathogen, anHHSSelect Agent, anNIH/NIAID Category A Priority Pathogen, aCDC Category A Bioterrorism Agent, and a Biological Agent for Export Control by theAustralia Group.[5]
Expression of the matrix protein VP40 is sufficient to generatevirus-like particles (no viral genetic material) in amammalian host that are remarkably indistinguishable from live virus, from a morphological standpoint.[5]
During and after the 2014-2016West African Ebola virus epidemic treatment options were sought; among them were the VP40 matrix protein as a target for possible research that may (or may not) lead to a therapeutic option.[6][7]