Specific Antiviral Activity Demonstrated by TGTP, A Member of a New Family of Interferon-Induced GTPases

• Published in: The Journal of immunology (1950) Vol. 161; no. 5; pp. 2348 - 2355
• Main Authors: Carlow, Douglas Alan, Teh, Soo-Jeet, Teh, Hung-Sia
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-09-1998
• Subjects: Animals; Antiviral Agents - pharmacology; DNA, Complementary - genetics; Enzyme Induction - drug effects; Enzyme Induction - immunology; GTP Phosphohydrolases - biosynthesis; GTP Phosphohydrolases - genetics; GTP Phosphohydrolases - metabolism; GTP-Binding Proteins - biosynthesis; GTP-Binding Proteins - genetics; GTP-Binding Proteins - physiology; Interferon-alpha - pharmacology; Interferon-gamma - pharmacology; Interferons - pharmacology; L Cells (Cell Line); Mice; Monomeric GTP-Binding Proteins; Receptors, Antigen, T-Cell - physiology; Recombinant Fusion Proteins - metabolism; SAM Domain and HD Domain-Containing Protein 1; Simplexvirus - drug effects; Simplexvirus - growth & development; Transfection - immunology; Vesicular stomatitis Indiana virus - drug effects; Vesicular stomatitis Indiana virus - growth & development; Viral Plaque Assay
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.161.5.2348

The GTPase superfamily includes a diversity of molecules whose functions are regulated through the binding and hydrolysis of GTP. This superfamily can be segregated into families of functionally related molecules that typically share amino acid sequence similarity within and around the nucleotide-binding domains. A new family of putative GTPases, including IRG-47, LRG-47, IGTP, and TGTP/Mg21, has recently emerged that share significant sequence identity (25-40%). Expression of these molecules has been shown to be selectively induced by IFN-gamma and in some cases by IFN-alpha beta or bacterial LPS. This induction pattern implicates these putative GTPases as part of the innate defense of cells to infection, but their role in such defense has not yet been defined. We have previously described the cloning of TGTP and now confirm its intrinsic activity as a GTPase. We found that TGTP is strongly induced by endogenous IFN-alpha beta produced in response to standard lipofection of plasmid DNA or polyinosinic polycytidylic acid. The ability of endogenously produced IFN-alpha beta to efficiently induce expression of TGTP under these conditions suggested that TGTP might participate in defense against viral infection. This proposal was borne out when TGTP-transfected L cells displayed relative resistance to plaque formation by vesicular stomatitis virus but not herpes simplex virus. This observation places TGTP among a small family of innate antiviral agents and has implications for the functions of other members of this family of GTPases.