Epstein-Barr Virus IL-10 Engages IL-10R1 by a Two-step Mechanism Leading to Altered Signaling Properties

Koi Herpesvirus Encodes and Expresses a Functional Interleukin-10

“…This, and their very different locations in the viral genomes (3,56), suggests that alloherpesvirus IL-10s may have arisen from independent gene capture events and that each has undergone rapid divergent evolution since capture from the host genome. Similar patterns of divergence from host IL-10 sequences have been observed among certain mammalian herpesvirus and poxvirus IL-10 orthologs (49), and this appears to have been driven by functional adaptations that modify their interaction with the host IL-10 receptor, resulting in altered signaling profiles (15,60). There is abundant evidence for a very dynamic genetic interaction between large DNA viruses and their hosts in evolutionary time scales through processes that can result in both the capture and loss of genes (20,24,49).…”

The Molecular Basis of IL-10 Function: from Receptor Structure to the Onset of Signaling

“…Despite these observations, no significant differences in biological activity have been found between cmvIL-10 and cIL-10. Interestingly, cIL-10 and ebvIL-10, which share identical complex structures, have markedly different biological activities (Ding et al 2001; Liu et al 1997; Rousset et al 1992; Yoon et al 2012). In the case of ebvIL-10, the functional differences between ebvIL-10 and cIL-10 are largely due to ebvIL-10’s reduced binding affinity for IL-10R1 and not large structural changes in the receptor complex (Ding et al 2001; Liu et al 1997; Yoon et al 2005).…”

“…On a biacore chip surface, the K D of the cIL-10/IL-10R1 interaction was determined to be 240pM (Yoon et al 2012). Thus, cell surface binding and in vitro surface plasmon resonance (SPR) analyses are in good agreement.…”

“…Not surprisingly, changes in site 1 (IL-10/IL-10R1) or site 2 (IL-10/IL-10R2) interfaces result in different biological outcomes (Ding et al 2001; Raftery et al 2004; Yoon et al 2012; Yoon et al 2006). Disruptions in IL-10 site 1, increases the effective concentration of the ligand required to induce one half of measured maximal biological responses (EC50).…”

“…Disruptions in IL-10 site 1, increases the effective concentration of the ligand required to induce one half of measured maximal biological responses (EC50). Despite increased EC50 values, site 1 mutants can still induce biological responses equivalent to cIL-10, at high protein concentrations (Yoon et al 2012). In contrast, mutations in IL-10 site 2 cannot induce the same response levels observed for cIL-10, despite the addition of extremely high protein concentrations (Yoon et al 2006).…”