{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nOAS3 is an interferon‐inducible enzyme that plays a central role in innate antiviral defense. Upon binding long double‐stranded RNA, OAS3 catalyzes the synthesis of 2′–5′ oligoadenylates that in turn activate the latent ribonuclease RNase L, triggering degradation of viral RNA and consequently inhibiting replication of a variety of viruses including West Nile, HCV, dengue, and enteroviruses. Notably, structural studies reveal that compared with its family members, OAS3 exhibits a higher affinity for dsRNA and produces oligoadenylates of optimal length for RNase L activation despite generating relatively shorter oligomers from ATP, thereby serving as a potent sensor and effector in antiviral responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies have revealed that single nucleotide polymorphisms and rare coding mutations in the OAS3 gene are associated with variable clinical outcomes in several viral infections. For instance, OAS3 variants have been implicated in altered susceptibility or disease progression in tick‐borne encephalitis, dengue virus infection with serotype‐dependent effects, hepatitis B and E virus infections, and enterovirus 71 infection, as well as in the modulation of interferon‐alpha treatment responses. In addition, while some reports underscore a strong antiviral role for OAS3, others indicate that subtle changes in its activity through host polymorphisms may affect the regulation of downstream antiviral effectors and inflammatory mediators. Together, these observations highlight that optimal OAS3 function is critical for balancing effective viral clearance with host inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classic antiviral role, recent evidence suggests that OAS3 may modulate broader aspects of the immune response. Studies in human macrophages have shown that loss of OAS3 can lead to the enhanced expression of chemokines and interferon‐responsive genes, indicating a regulatory function in controlling inflammation. Moreover, interactions with cellular proteins such as C11orf83 point to a novel mechanism whereby metabolic components interface with the OAS3–RNase L pathway to specifically target exogenous RNA for degradation, thus fine‐tuning antiviral surveillance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ara G Hovanessian, Just Justesen "}, {"type": "b", "children": [{"type": "t", "text": "The human 2'-5'oligoadenylate synthetase family: unique interferon-inducible enzymes catalyzing 2'-5' instead of 3'-5' phosphodiester bond formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochimie (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biochi.2007.02.003"}], "href": "https://doi.org/10.1016/j.biochi.2007.02.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17408844"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17408844"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Young-Chan Kwon, Ju-Il Kang, Soon B Hwang, et al. 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