Virus maturation by budding

Enveloped viruses mature by budding at cellular membranes. It has been gene rally thought that this process is driven by interactions between the viral transmembrane proteins and the internal virion components (core, capsid, o r nucleocapsid). This model was particularly applicable to alphaviruses, wh ich require both spike proteins and a nucleocapsid for budding However, gen eric studies have clearly shown that the retrovirus core protein, i.e., the Gag protein, is able to form enveloped pal-rides by itself Also budding of negative-strand RNA viruses (rhabdoviruses, orthomyxoviruses, and paramyxo viruses) seems to be accomplished mainly by internal components, most proba bly the matrix protein, since the spike proteins are not absolutely require d for budding of these vir roes either: In contrast, budding of coronavirus particles can occur in the absence of the nucleocapsid and appears to requ ire two membrane proteins only. Biochemical and structural data suggest tha t the proteins which play a key role in budding, drive this process by form ing a three-dimensional (cage-like) protein lattice at the surface of or wi thin the membrane. Similarly, recent electron microscopic studies revealed that the alphavirus spike proteins are also engaged in extensive lateral in teractions, forming a dense protein shell at the outer surface of the viral envelope. On the basis of these data, we propose that the budding of envel oped viruses in general is governed by lateral interactions between periphe ral ol integral membrane proteins. This new concept also provides answers t o the question of how viral and cellular membrane proteins are sorted durin g budding. In addition, it has implications for the mechanism by which the virion is uncoated during virus entry.