Viral budding via the host ESCRT complexes (kw:KW-1187)


Many enveloped viruses recruit components of the cellular ESCRT (endosomal sorting complex required for transport) system to mediate host-assisted viral budding .

ESCRT complexes are normally used by the cell for biological functions involving membrane remodeling, such as intraluminal vesicle formation, autophagy or terminal stages of cytokinesis . The ESCRT family consists of ESCRT-0, ESCRT-I, ESCRT-II which are primarily involved in cargo sorting and membrane deformation, and ESCRT-III which cleaves the bud neck from its cytosolic face . In the last step, vps4 disassembles the complex. The budding reaction catalyzed by the ESCRT machinery has reversed topology when compared with most other budding processes in the cell, such as endocytosis and formation of transport vesicles.

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Specific motifs in viral proteins called late assembly domains (L-domains) are responsible for recruiting the host ESCRT machinery directly or via ESCRT-associated proteins like ALIX.
- P(T/S)AP motif recruits the ESCRT machinery via TSG101.
- PPxY motif enlists members of the NEDD4 family of ubiquitin ligases through interactions with WW domains, although the precise link between the NEDD4-like proteins and the ESCRT machinery is still unknown.
- ΘPxV where Θ is a hydrophobic amino acid.
- YP(x)n L binds the adaptor protein ALIX, which in turn binds and recruits the ESCRT machinery.

Some enveloped viruses however seem to use other mechanisms to bud, as it has been shown for Influenza virus .

Viruses budding through the ESCRT machinery:

Family Virus Viral protein L-domain motif Host ESCRT Budding location ref
Retroviridae HIV-1 P6-gag PTAP TSG101 Cell membrane
LYPx<sub>nL ALIX (low affinity) Cell membrane
SIV P6-gag PTAP TSG101 Cell membrane
LYPx<sub>nL ALIX Cell membrane
HTLV-1 P19-gag PPxY NEDD4 Cell membrane
PTAP TSG101 (low affinity) Cell membrane
Human spumaretrovirus Gag protein PTAP TSG101 Cell membrane
Moloney murine leukemia virus P12-gag PPxY ITCH Cell membrane
PTAP TSG101 Cell membrane
LYPx<sub>nL ALIX Cell membrane
Bovine leukemia virus Gag protein PPxY<sub>nL NEDD4 Cell membrane
Rous sarcoma virus Gag protein PPxY NEDD4 Cell membrane
Mason-Pfizer monkey virus Gag protein PSAP TSG101 Cell membrane
PPxY NEDD4 Cell membrane
EIAV P9-gag LYPx<sub>nL ALIX Cell membrane
Hepadnaviridae HBV ? Capsid protein ? ALIX Endoplasmic reticulum
Filoviridae Ebolavirus Matrix protein PTAP TSG101 Cell membrane
PPxY NEDD4 Cell membrane
Marburgvirus Matrix protein PPxY NEDD4 Cell membrane
Nucleoprotein PSAP TSG101 Cell membrane
Rhabdoviridae Vesicular stomatitis virus M protein PPxY NEDD4 Cell membrane
?PSAP ? TSG101 Cell membrane
Rabies virus M protein PPxY NEDD4 Cell membrane
Paramyxoviridae Sendai virus M protein YLDL ALIX Cell membrane
Newcastle disease virus M protein FPIV ? Cell membrane
Nipah virus M protein YMYL ALIX Cell membrane
C protein ? TSG101 Cell membrane
Simian virus 5 M protein FPIV ? Cell membrane
Mumps virus M protein FPVI ? Cell membrane
Arenaviridae Lymphocytic choriomeningitis virus Z protein PPPY NEDD4 Cell membrane
? ? TSG101 Cell membrane
Lassa virus Z protein PTAP TSG101 Cell membrane
PPxY NEDD4 Cell membrane
Bunyaviridae Gn glycoproteins ?YxxL ? ALIX Golgi
Flaviviridae Hepatitis C virus ? Core protein ? ? Endoplasmic reticulum
Herpesviridae Herpes simplex virus 1 ? ? Vps4 Trans-Golgi
Epstein-Barr virus ? ? ? Trans-Golgi
HCMV ? ? Vps4 Trans-Golgi
Poxviridae Vaccinia virus F13 protein LYPx(n)L ? Cell membrane

Matching UniProtKB/Swiss-Prot entries

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