{'fraction_non_alphanumeric': 0.024407252440725245, 'fraction_numerical': 0.030683403068340307, 'mean_word_length': 5.40625, 'pattern_counts': {'":': 0, '<': 1, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
S27 of IFNα1 Contributes to Its Low Affinity for IFNAR2 and Weak Antiviral Activity.

Type I interferons (IFNs) signal by forming a high affinity IFN-IFNAR2 dimer, which subsequently recruits IFNAR1 to form a ternary complex that initiates JAK/STAT signaling. Among the 12 IFNα subtypes, IFNα1 has a uniquely low affinity for IFNAR2 (<100 × of the other IFNα subtypes) and commensurately weak antiviral activity, suggesting an undefined function distinct from suppression of viral infections. Also unique in IFNα1 is substitution of a serine for phenylalanine at position 27, a contact point that stabilizes the IFNα:IFNAR2 hydrophobic interface. To determine whether IFNα1-S27 contributes to the low affinity for IFNAR2, we created an IFNα1 mutein, IFNα1-S27F, and compared it to wild-type IFNα1 and IFNα2. Substitution of phenylalanine for serine increased affinity for IFNAR2 ∼4-fold and commensurately enhanced activation of STAT1, STAT3, and STAT5, transcription of a subset of interferon stimulated genes, and restriction of vesicular stomatitis virus infection in vitro. Structural modeling suggests that S27 of IFNα1 disrupts the IFNα:IFNAR2 hydrophobic interface that is otherwise stabilized by F27 and that replacing S27 with phenylalanine partially restores the hydrophobic surface. Disruption of the hydrophobic IFNα:IFNAR2 interface by the unique S27 of IFN α1 contributes to its low affinity and weak antiviral activity.