HCMV IL-10 Suppresses Cytokine Expression in Monocytes Through Inhibition of Nuclear Factor- κ B

Abstract

Modulation of host immune responses is a common strategy for promoting virus persistence and avoiding clearance. Human cytomegalovirus (HCMV) is known to encode numerous immunomodulatory genes, including a homolog of the cytokine human interleukin-10 (hIL-10). While having limited sequence homology to hIL-10, cytomegalovirus IL-10 (cmvIL-10) shares many functional characteristics with the human cytokine and acts as a potent suppressor of the inflammatory immune response. The mechanism by which hIL-10 inhibits inflammatory cytokines involves a transcriptional block via inhibition of nuclear factor-κB (NF-κB) activity. To determine whether cmvIL-10 employs the same mechanism to inhibit cytokine production, the effect of cmvIL-10 on NF-κB signaling in monocytes was investigated. The results demonstrate that cmvIL-10 does inhibit NF-κB activation, as evidenced by reduced degradation of the NF-κB inhibitor IκB-α, and decreased transcription of the NF-κB–responsive genes tumor necrosis factor-α (TNF-α) and IL-1β. These studies confirm that cmvIL-10 mediates cytokine suppression by blocking NF-κB transcriptional activity in human monocytes.