Animal and bacterial viruses share conserved mechanisms of immune evasion

Affiliations

• Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
• Gladstone-UCSF Institute of Data Science and Biotechnology, San Francisco, CA 94158, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
• Gladstone-UCSF Institute of Data Science and Biotechnology, San Francisco, CA 94158, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
• Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Electronic address: philip_kranzusch@dfci.harvard.edu.

PMID:  39197447  DOI: 10.1016/j.cell.2024.07.057

Abstract

Animal and bacterial cells sense and defend against viral infections using evolutionarily conserved antiviral signaling pathways. Here, we show that viruses overcome host signaling using mechanisms of immune evasion that are directly shared across the eukaryotic and prokaryotic kingdoms of life. Structures of animal poxvirus proteins that inhibit host cGAS-STING signaling demonstrate architectural and catalytic active-site homology shared with bacteriophage Acb1 proteins, which inactivate CBASS anti-phage defense. In bacteria, phage Acb1 proteins are viral enzymes that degrade host cyclic nucleotide immune signals. Structural comparisons of poxvirus protein-2'3'-cGAMP and phage Acb1-3'3'-cGAMP complexes reveal a universal mechanism of host nucleotide immune signal degradation and explain kingdom-specific additions that enable viral adaptation. Chimeric bacteriophages confirm that animal poxvirus proteins are sufficient to evade immune signaling in bacteria. Our findings identify a mechanism of immune evasion conserved between animal and bacterial viruses and define shared rules that explain host-virus interactions across multiple kingdoms of life.

动物和细菌细胞通过进化保守的抗病毒信号通路感知并防御病毒感染。在这里，我们展示了病毒如何利用免疫逃逸机制克服宿主信号，这些机制在真核生物和原核生物的生命王国之间直接共享。动物痘病毒蛋白的结构抑制宿主cGAS-STING信号，显示出与使CBASS抗病毒防御失效的细菌噬菌体Acb1蛋白在结构和催化活性位点上的同源性。在细菌中，噬菌体Acb1蛋白是降解宿主环核苷酸免疫信号的病毒酶。痘病毒蛋白-2'3'-cGAMP和噬菌体Acb1-3'3'-cGAMP复合物的结构比较揭示了一种宿主核苷酸免疫信号降解的普遍机制，并解释了使病毒适应的特定于王国的附加特征。嵌合噬菌体确认动物痘病毒蛋白足以在细菌中逃逸免疫信号。我们的研究发现了动物病毒和噬菌体之间保留的免疫逃逸机制，并定义了解释多个生命王国中宿主-病毒相互作用的共同规则。