Enveloped viruses complete their replication cycle by budding from the host cell plasma membrane. After assembly of viral proteins on the membrane surface and incorporation of genetic material, enveloped viruses deform the plasma membrane and subsequently pinch off by membrane fission. Several host cell proteins are involved in the budding process.
The assembly of retroviruses like human immunodeficiency virus (HIV) takes place by viral processing of the Gag protein and occurs at the endosomal and plasma membrane. On the other hand filoviruses like Ebola and Marburg assemble at the plasma membrane by a process mediated by endosomal complexes required for transport (ESCRT). The ESCRT are components of the vacuolar sorting pathway which gives rise to multivesicular bodies (MVB). The host protein VPS4 plays an important role in recycling ESCRT complexes and thus activating the process of MVB formation.
Retroviruses and filoviruses have been shown to use the ESCRT pathway for their budding and release from the host cell. The late budding domains (L domains) in the Gag p6 protein of HIV and matrix protein VP40 of filoviruses are ubiquitinated by TSG101 of the ESCRT complex and NEDD4, respectively. Interaction of the ubiquitinated viral L domains with members of ESCRT facilitates vesicle formation within the endosome, followed by delivery to the plasma membrane. In case of filoviruses, in addition to VP40, surface glycoproteins and possibly the nucleocapsid proteins are transported via the ESCRT pathway to the plasma membrane, where assembly and budding occurs.
Membrane-bound proteins play a major role in viral particle release in the Orthopox family of viruses (Eg vaccinia virus). This virus exists in two distinct forms, namely the intracellular mature virus (IMV) and the intracellular enveloped virus (IEV), which differ in the number of membranes and their composition. Envelop proteins like F12L play a role in converting the IEV to a cell surface enveloped virus (CEV). Viral proteins like A34R and A36R induce the formation of an actin tail that exposes the CEV, while other envelope proteins such as B5R induce the release of extracellular enveloped virus (EEV).
In the case of influenza viruses, the matrix protein M1 plays a crucial role in budding. Viral ribonucleoprotein (vRNP) is transported out of the nucleus complexed with M1 protein. In addition, M1 forms a bridge between surface proteins like HA, NA and vRNP in the trans Golgi network; the resultant complex is transported to the plasma membrane where assembly and budding take place. The surface protein NA is responsible for viral particle release.
The assembly and budding of the Herpes virus in the nucleus is initiated by two viral proteins UL31 and UL34. These proteins are components of a primary envelop and initiate budding in the perinuclear space aided by host proteins protein PKC and Lamin B. Following de-envelopment and release into the cytoplasm, the viral capsid acquires several tegument proteins such as UL36, UL37, UL20 and UL48, which interact with viral glycoproteins that are components of golgi derived vesicles. This interaction results in secondary envelopment, followed by release into the extracellular space.
This pathway highlights a few mechanisms of exit adopted by enveloped viruses.