Details

Autor(en) / Beteiligte

• Izumida, Mai
• Hayashi, Hideki
• Smith, Chris
• Ishibashi, Fumito
• Suga, Koushirou
• Kubo, Yoshinao

Titel

Antivirus activity, but not thiolreductase activity, is conserved in interferon-gamma-inducible GILT protein in arthropod

Ist Teil von

• Molecular immunology, 2021-12, Vol.140, p.240-249

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• •Thiolreductase active motif of mammalian GILT protein is CXXC, but the GILT homolog of black tiger shrimp has CXXS.•Black tiger shrimp GILT does not have thiolreductase activity.•Black tiger shrimp GILT inhibits virus infection through complex formation with the viral envelope protein.•The common function of GILT homologs in mammalians and lower animals is antiviral activity. We have previously reported that gamma-interferon inducible lysosomal thiolreductase (GILT) functions as a host defense factor against retroviruses by digesting disulfide bonds on viral envelope proteins. GILT is widely conserved even in plants and fungi as well as animals. The thiolreductase active site of mammalian GILT is composed of a CXXC amino acid motif, whereas the C-terminal cysteine residue is changed to serine in arthropods including shrimps, crabs, and flies. GILT from Penaeus monodon (PmGILT) also has the CXXS motif instead of the CXXC active site. We demonstrate here that a human GILT mutant (GILT C75S) with the CXXS motif and PmGILT significantly inhibit amphotropic murine leukemia virus vector infection in human cells without alterning its expression level and lysosomal localization, showing that the C-terminal cysteine residue of the active site is not required for the antiviral activity. We have reported that human GILT suppresses HIV-1 particle production by digestion of disulfide bonds on CD63. However, GILT C75S mutant and PmGILT did not digest CD63 disulfide bonds, and had no effect on HIV-1 virion production, suggesting that they do not have thiolreductase activity. Taken together, this study found that antiviral activity, but not thiolreductase activity, is conserved in arthropod GILT proteins. This finding provides a new insight that the common function of GILT is antiviral activity in many animals.