Viroids are very small, unencapsidated RNAs that replicate and induce severe disease in plants without encoding for any proteins. The mechanisms by which the viroid RNA regulates these events and interacts with host factors are unknown. An Mr 68,000 host-encoded protein has been identified that is differentially phosphorylated in extracts from viroid-infected and mock-inoculated tissues. This phosphoprotein is immunologically related to a double-stranded (ds) RNA-dependent protein kinase from virus-infected, interferon-treated human cells. Further, nucleotide photoaffinity labeling indicates that the protein has an ATP binding site. This protein is similar to dsRNA-dependent protein kinases implicated in mammalian systems in the regulation of protein synthesis and virus replication.

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Highly conserved enkephalin containing peptides (ECPs) are selectively processed from proenkephalin, which is synthesized in both the neuroendocrine and immune systems. The reported regulatory effects within the central nervous system and the biologic release patterns from both activated lymphocytes and stimulated adrenal chromaffin cells suggest the ECPs may act as regulatory factors of the immune system. We tested the effects of three of the ECPs, Peptides F, E, and B, on the in vitro Ab-forming cell (AFC) response murine splenocytes to antigenic challenge. In contrast to the immunosuppressive effects of the pentapeptide enkephalins, physiologic concentrations of the ECPs significantly enhanced the AFC response to both T cell-dependent and T cell-independent Ags. The effects are not sensitive to competition by the opiate receptor antagonist, naloxone, suggesting cell surface interactions that do not involve classical opiate receptors. These studies provide evidence that the effects are mediated through T cells rather than B cells. Peptide F-treated splenocytes also showed a significant enhancement of the AFC response to suboptimal Ag concentrations, suggesting a mechanism of action in which the ECPs may act to lower the threshold of activation of the effector cell. These results suggest that the ECPs are physiologically important modifiers of the humoral immune response. Given their release patterns and demonstrated action on the in vitro immune response, the proenkephalin-derived ECPs have the potential to be involved in both paracrine and autocrine regulatory networks within the immune system and as a positive immunoregulatory effect from the neuroendocrine system.