Meta-Biol

• Pathways

The human oligoadenylate synthetase (OAS) family consists of four proteins whose production is stimulated by interferon, OAS1, OAS2, OAS3, and OASL. The first three members have the 2'-5'-oligoadenylate synthetase activity for which the family is named (Sadler AJ & Williams BR 2008), whereas OASL is devoid of this activity despite sharing significant sequence similarity with the other OAS proteins (Zhu J et al. 2015). OAS1, 2, and 3 are activated by double-stranded RNA to synthesize 5'-triphosphorylated 2'-5'-oligoadenylates (2-5A) from ATP (Kerr IM & Brown RE 1978). The 2-5A serve as chemically unique second messengers that induce regulated RNA decay by activating ribonuclease L (RNase L), thus mediating antiviral innate immunity (Zhou A et al. 1993; Lin RJ et al. 2009; Huang H et al. 2014; Han Y et al. 2014). RNase L has also been implicated in antibacterial innate immunity (Li XL et al. 2008). RNase L cleaves single-stranded RNA (ssRNA) in U-rich sequences, typically after UU or UA dinucleotides leaving a 5'-OH and 2',3'-cyclic phosphate (Floyd-Smith G et al. 1981; Wreschner DH et al.1981; Cooper DA et al. 2014).

Some OAS proteins have additional or alternative antiviral functions that are independent of RNase L activity (Perelygin AA et al., 2002; Kristiansen H et al. 2011). The precise mechanisms of RNase L-independent OAS antiviral activities remain to be fully elucidated.

Cytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concentrations. Cytokines bind to specific membrane receptors, which then signal the cell via second messengers, to regulate cellular activity.

Humans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first critical hours and days of exposure to a new pathogen, our innate immune system.