BioProject

ISG15 is an IFN-α/β-inducible, ubiquitin-like intracellular protein. Its conjugation to various proteins (ISGylation) contributes to antiviral immunity in mice. More...

ISG15 is an IFN-α/β-inducible, ubiquitin-like intracellular protein. Its conjugation to various proteins (ISGylation) contributes to antiviral immunity in mice. We describe human patients with inherited ISG15 deficiency and mycobacterial but not viral diseases. The lack of intracellular ISG15 production and protein ISGylation is not associated with cellular susceptibility to any of the viruses tested, consistent with the lack of viral diseases in these patients. By contrast, the lack of mycobacterium-induced ISG15 secretion by leukocytes — granulocytes in particular — reduces the production of IFN-γ by lymphocytes, including NK cells in particular, accounting for mycobacterial disease. This experiment of Nature shows that human ISG15 is largely redundant as an IFN-α/β-inducible ubiquitin-like intracellular protein in antiviral immunity, but essential as an IFN-γ-inducing secreted molecule for anti-mycobacterial immunity. Less...