Abstract
The zinc metalloprotease ZMPSTE24 is a constitutively and ubiquitously expressed host restriction factor that is responsible for limiting infection by a broad spectrum of enveloped viruses, including influenza A, vesicular stomatitis, zika, ebola, Sindbis, cowpox, and vaccinia viruses, but not murine leukemia or adenovirus. Antiviral function is independent of ZMPSTE24 enzymatic activity. Protein interaction and genetic complementation studies indicate that ZMPSTE24 is a component of a common antiviral pathway that is associated with interferon-induced transmembrane proteins. In vivo studies with zmpste24-deficient mice demonstrate the importance of ZMPSTE24 for antiviral defense.
Keywords:
IFITM3 proteome; endosome; enveloped viruses; influenza; interferon; viral entry.
MeSH terms
-
Animals
-
Cell Membrane / drug effects
-
Cell Membrane / immunology*
-
Cell Membrane / virology
-
Endosomes / drug effects
-
Endosomes / immunology*
-
Endosomes / virology
-
Gene Expression Regulation
-
Genetic Complementation Test
-
HEK293 Cells
-
Host-Pathogen Interactions*
-
Humans
-
Immunity, Innate
-
Influenza A virus / drug effects
-
Influenza A virus / immunology
-
Interferon-gamma / pharmacology
-
Membrane Proteins / genetics*
-
Membrane Proteins / immunology
-
Metalloendopeptidases / genetics*
-
Metalloendopeptidases / immunology
-
Mice
-
Mice, Knockout
-
Protein Binding
-
Protein Interaction Mapping
-
RNA-Binding Proteins / genetics*
-
RNA-Binding Proteins / immunology
-
Signal Transduction
-
Virus Internalization / drug effects
Substances
-
IFITM3 protein, human
-
Membrane Proteins
-
RNA-Binding Proteins
-
Interferon-gamma
-
Metalloendopeptidases
-
ZMPSTE24 protein, human