Functional cross-species conservation of guanylate-binding proteins in innate immunity

Abstract

Guanylate binding proteins (GBPs) represent an evolutionary ancient protein family widely distributed among eukaryotes. They are interferon (IFN)-inducible guanosine triphosphatases that belong to the dynamin superfamily. GBPs are known to have a major role in the cell-autonomous innate immune response against bacterial, parasitic and viral infections and are also involved in inflammasome activation. Evolutionary studies depicted that GBPs present a pattern of gain and loss of genes in each family with several genes pseudogenized and some genes more divergent, indicative for the birth-and-death evolution process. Most species harbor large GBP gene clusters encoding multiple paralogs. Previous functional studies mainly focused on mouse and human GBPs, but more data are becoming available, broadening the understanding of this multifunctional protein family. In this review, we will provide new insights and give a broad overview about GBP evolution, conservation and their roles in all studied species, including plants, invertebrates and vertebrates, revealing how far the described features of GBPs can be transferred to other species.

Interferon inducible guanylate‐binding protein 1 modulates the lipopolysaccharide‐induced cytokines/chemokines and mitogen‐activated protein kinases in macrophages

“…44,54 GBPs are a family of IFN-inducible proteins that play crucial roles in the innate immune response against intracellular pathogens. 55 These proteins are primarily known for targeting and disrupting the replication of various intracellular pathogens, including bacteria, viruses, and protozoa. 35,56 LPS is a major component of different types of Gram-negative bacteria and is involved in their pathogenesis; therefore, by using quantitative real-time PCR, we measured the time-dependent expression level of GBPs (GBP1-7) in vitro in the presence of LPS.…”

“…Activated macrophages are a heterogeneous collection of cells with diverse functions such as secretion of inflammatory mediators, intracellular pathogen killing, and induction of cytotoxic T and helper T cell responses 44,54 . GBPs are a family of IFN‐inducible proteins that play crucial roles in the innate immune response against intracellular pathogens 55 . These proteins are primarily known for targeting and disrupting the replication of various intracellular pathogens, including bacteria, viruses, and protozoa 35,56 .…”

Guanylate-binding protein 1 inhibits inflammatory factors produced by H5N1 virus through Its GTPase activity

“…GBP1 has an elongated carboxy-terminal region with a series of amphipathic helices for protein-lipid and protein-protein interactions ( Prakash et al, 2000 ). GBPs strongly influence cell-autonomous innate immune responses against bacterial, parasitic, and viral infections and are also involved in inflammasome activation ( Schelle et al, 2023 ).…”

Human FAM111A inhibits vaccinia virus replication by degrading viral DNA-binding protein I3 and is antagonized by poxvirus host range factor SPI-1

“…Upon viral infection, cells initiate various programs, such as the induction of type I interferons and the expression of an armory of antiviral factors that can restrict viral invasion, gene expression, DNA replication, and virion assembly. More recent findings point to the fact that some host defense factors are multifunctional and can display potent antiviral activity in a way that is distinct from their regular cellular functions [1][2][3][4] . One such example is FAM111A (family with sequence similarity 111 member A), a protein found exclusively in mammals harboring a fully functional trypsin-like C-terminal protease domain 5 .…”