VP40

VP40 is a 40-kilodalton matrix protein encoded by the VP40 gene of filoviruses, most notably Ebola virus and Marburg virus. It plays a central role in virion assembly and budding and can drive particle release when expressed in cells.

Structure and localization: VP40 is a peripheral membrane protein that associates with the inner leaflet of the plasma membrane. Its targeting is aided by a cluster of basic residues and interactions with anionic lipids such as phosphatidylserine. In solution, VP40 can form dimers and higher-order oligomers that assemble into a matrix beneath the viral envelope.

Function: The protein participates in virion assembly by linking the nucleocapsid complex to the budding site and by shaping the matrix that underlies the envelope. It promotes particle morphogenesis, contributing to the characteristic filamentous virions of filoviruses.

Late domains and budding: VP40 contains late-domain motifs, often PTAP and PPEY, that recruit host ESCRT machinery, including Tsg101 and Nedd4 family ligases, to mediate budding and membrane scission at the plasma membrane.

Virus-like particle formation and research use: Expression of VP40 alone can induce the release of filamentous virus-like particles, making VP40 a useful model for studying budding. Mutations that disrupt lipid binding or late-domain function markedly reduce budding efficiency.

Clinical relevance: Because VP40 is essential for budding, it is a frequent target of antiviral research aimed at blocking virus release and spread.