Guanylate-binding proteins in virus infection

Guanylate-binding proteins (GBPs) are immune GTPases that are induced in response to interferon stimulation/pathogen infection. These proteins arose early in evolution and have multiple physiological roles ranging from tumor suppression to anti-microbial func-tions. While several studies describe their mechanistic role in the lysis of bacteria/patho-gen vacuole, and activation of the inflammasome, their functions in viral infections are only just emerging. The role of the GBPs in virus infections is multifaceted, being both dependent on and independent of GTP binding/hydrolysis and isoprenylation. Diverse antiviral roles are documented such as inhibition of viral RNA/protein synthesis, block of viral envelope glycoprotein processing, and targeting viral protein for degradation. Not surprisingly, several viral proteins bind to specific GBPs and antagonize their antiviral effects. While recruitment of GBP1, Gbp1, Gbp2 on the virus replication complex has been reported, the functional implications of this are not entirely clear. Furthermore, their role in interferon and inflammation activation during virus infection are contradictory, with reports of both positive and negative regulation. Here, we discuss the emerging functional roles of GBPs in virus infections.

Automated summary

Guanylate-binding proteins (GBPs) are immune GTPases induced by interferon and are involved in various physiological processes. They play important roles in bacterial and viral infections, but their functions in viral infections are still not well understood. GBPs have diverse antiviral roles including inhibition of viral replication, blocking of viral protein processing, and targeting viral proteins for degradation. However, viral proteins can also counteract the antiviral effects of GBPs. This review discusses the emerging functional roles of GBPs in viral infections.