Table 1.
Characteristics of intrinsic inhibitors of enveloped virus entry
| Intrinsic inhibitor | Entry step inhibited | Mechanism or mechanisms | Human enveloped viruses targeted | Cell types expressed | Subcellular localization | Induction |
|---|---|---|---|---|---|---|
| IFITM1, IFITM2, IFITM3 | Membrane fusion or endocytic trafficking | Membrane modulation (rigidity, curvature), endosome redirection and virion degradation | VSV, IAV, DENV, ZIKV, HCV, YFV, WNV, EBOV, RVFV, CHIKV, HIV-1, hCoV-229E, SARS-CoV, MERS-CoV, SARS-CoV-2 | Ubiquitous | Plasma membrane, endomembranes (transmembrane) | Constitutive, type I interferons, type II interferon, LPS, IL-6, TGFβ |
| ZMPSTE24 | Membrane fusion | Cooperation with IFITM proteins | VSV, IAV, LCMV, LASV, CPXV, VACV | Ubiquitous | Nuclear envelope, endomembranes (transmembrane) | Constitutive |
| CH25H | Membrane fusion | Membrane modulation via product 25HC (rigidity, curvature, cholesterol depletion) | VSV, EBOV, HIV-1, ZIKV, RVFV, HSV, NiV, SARS-CoV-2 | Immune cells, epithelial cells | Endoplasmic reticulum (transmembrane) | Type I interferons, type II interferon |
| LY6E | Cell attachment or membrane fusion | Receptor downmodulation or endosome redirection | DENV, ZIKV, YFV, WNV, HIV-1, hCoV-229E, hCoV-OC43, SARS-CoV, MERS-CoV, SARS-CoV-2 | Immune cells, epithelial cells | Plasma membrane | Retinoic acid, type I interferons |
| NCOA7 | Viral glycoprotein activation | Enhanced cathepsin activity (virion degradation) | VSV, IAV, HCV | Immune cells, nervous cells, epithelial cells | Nucleus, endomembranes | Type I interferons |
| GILT | Viral glycoprotein activation | Inhibition of cathepsin activity | EBOV, LASV, HIV-1, SARS-CoV | Immune cells | Cytosol, endomembranes (lumen) | Constitutive, type II interferon |
| CD74 | Viral glycoprotein activation | Inhibition of cathepsin activity | EBOV, SARS-CoV-2 | Immune cells | Plasma membrane, endomembranes (transmembrane) | LPS, type II interferon |
| ADAP2 | Endocytic trafficking | Endosome redirection and virion degradation | VSV, DENV | Ubiquitous | Cytosol | Type I interferons |
25HC, 25-hydroxycholesterol; ADAP2, ARFGAP with dual pleckstrin homology domain-containing protein 2; CH25H, cholesterol 25-hydroxylase; CHIKV, chikungunya virus; CPXV, cowpox virus; DENV, dengue virus; EBOV, Ebola virus; GILT, interferon-γ-inducible lysosomal thiol reductase; hCoV-229E, human coronavirus 229E; hCoV-OC43, human coronavirus OC43; HCV, hepatitis C virus; HSV, herpes simplex virus; IAV, influenza A virus; IFITM, interferon-induced transmembrane protein; LASV, Lassa virus; LCMV, lymphocytic choriomeningitis virus; LPS, lipopolysaccharide; LY6E, lymphocyte antigen 6E; MERS-CoV, Middle East respiratory syndrome coronavirus; NCOA7, nuclear receptor co-activator protein 7; NiV, Nipah virus; RVFV, Rift Valley fever virus; SARS-CoV, severe acute respiratory syndrome coronavirus; VACV, vaccinia virus; VSV, vesicular stomatitis virus; WNV, West Nile virus; YFV, yellow fever virus; ZIKV, Zika virus; ZMPSTE24, zinc metalloproteinase STE24.