Chinese tree shrews (Tupaia belangeri chinensis) are increasingly used as an alternative experimental animal to non-human primates in studying viral infections. Guanylate-binding proteins (GBP) belong to interferon (IFN)-inducible GTPases and defend the mammalian cell interior against diverse invasive pathogens. Previously, we identified five tree shrew GBP genes (tGBP1, tGBP2, tGBP4, tGBP5, and tGBP7) and found that tGBP1 showed antiviral activity against vesicular stomatitis virus (VSV) and type 1 herpes simplex virus (HSV-1) infections. Here, we showed that the anti-VSV activity of tGBP1 was independent of its GTPase activity and isoprenylation. In response to VSV infection, instead of regulating IFN expression and autophagy, tGBP1 competed with the VSV nucleocapsid (N) protein in binding to the VSV phosphoprotein (VSV-P), leading to the repression of the primary transcription of the VSV genome. These observations constitute the first report of the potential mechanism underlying the inhibition of VSV by GBP1.
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