African Swine Fever Virus EP364R and C129R Target Cyclic GMP-AMP To Inhibit the cGAS-STING Signaling Pathway.

African swine fever virus (ASFV) is a highly pathogenic swine DNA virus with high mortality that causes African swine fever (ASF) in domestic pigs and wild boars. For efficient viral infection, ASFV has developed complex strategies to evade key components of antiviral innate immune responses. However, the immune escape mechanism of ASFV remains unclear. Upon ASFV infection, cyclic GMP-AMP (2',3'-cGAMP) synthase (cGAS), a cytosolic DNA sensor, recognizes ASFV DNA and synthesizes the second messenger 2',3'-cGAMP, which triggers interferon (IFN) production to interfere with viral replication. In this study, we demonstrated a novel immune evasion mechanism of ASFV EP364R and C129R, which blocks cellular cyclic 2',3'-cGAMP-mediated antiviral responses. ASFV EP364R and C129R with nuclease homology inhibit IFN-mediated responses by specifically interacting with 2',3'-cGAMP and exerting their phosphodiesterase (PDE) activity to cleave 2',3'-cGAMP. Particularly notable is that ASFV EP364R had a region of homology with the stimulator of interferon genes (STING) protein containing a 2',3'-cGAMP-binding motif and point mutations in the Y76S and N78A amino acids of EP364R that impaired interaction with 2',3'-cGAMP and restored subsequent antiviral responses. These results highlight a critical role for ASFV EP364R and C129R in the inhibition of IFN responses and could be used to develop ASFV live attenuated vaccines. IMPORTANCE African swine fever (ASF) is a highly contagious hemorrhagic disease in domestic pigs and wild boars caused by African swine fever virus (ASFV). ASF is a deadly epidemic disease in the global pig industry, but no drugs or vaccines are available. Understanding the pathogenesis of ASFV is essential to developing an effective live attenuated ASFV vaccine, and investigating the immune evasion mechanisms of ASFV is crucial to improve the understanding of its pathogenesis. In this study, for the first time, we identified the EP364R and C129R, uncharacterized proteins that inhibit type I interferon signaling. ASFV EP364R and C129R specifically interacted with 2',3'-cGAMP, the mammalian second messenger, and exerted phosphodiesterase activity to cleave 2',3'-cGAMP. In this study, we discovered a novel mechanism by which ASFV inhibits IFN-mediated antiviral responses, and our findings can guide the understanding of ASFV pathogenesis and the development of live attenuated ASFV vaccines.

Spirosoma areae sp. nov., Isolated from Soil.

A yellow-colored Gram-negative strain, Arct 1-12T, was isolated from a soil sample collected in Seoul Women's University, South Korea, and grown on R2A agar at 25 °C. Growth of strain Arct 1-12T was observed at a temperature range of 15-30 °C (optimal 25 °C), but not at 4 or 42 °C. The strain tolerated up to 1% NaCl (w/v) and displayed optimal growth in the absence of NaCl. Growth occurred at pH 6.0-9.0 (optimally at pH 7). According to the 16S rRNA gene sequence, the strain is moderately related to Spirosoma spitsbergense DSM 19989T (93.54%), S. endophyticum EX36T (93.25%), S. linguale LMG 10896T (92%), S. luteum DSM 19990T (93.16%), S. panaciterrae DSM 21099T (91.09%), S. oryzae RHs22T (90.37%), and S. rigui WPCB118T (91.54%). Chemotaxonomic analyses revealed that strain Arct 1-12T possesses MK-7 as the predominant menaquinone, a polar lipid profile consisting of phosphatidylethanolamine, an unknown aminolipid, an unknown aminophospholipid, and an unknown lipid, and iso-C15:0, C16:1 ω5c and Summed Feature 3 (C16:1 ω6c and/or C16:1 ω7c) as the major fatty acids. The DNA G+C content is 52.3 mol %. Based on polyphasic evidence, strain Arct 1-12T (=JCM 31025 T = KCTC 42814T) is classified as the type strain of a novel Spirosoma species for which the name Spirosoma areae sp. nov. is proposed.