Human cytomegalovirus (HCMV) infection induces both innate and adaptive immune responses, and whilst these responses ultimately lead to the resolution of productive infection, the clearance of replicating virus can take weeks or months. The capacity of HCMV to interfere with immune-mediated clearance is likely due to viral genes that target host immune responses, including a viral homologue of human interleukin-10 (hIL-10), termed cmvIL-10, which exerts a number of immunomodulatory functions. We have previously reported that cmvIL-10 downregulates surface MHC Class II (MHC II), which was associated with decreased transcription of the master regulator of MHC II genes, the class II transactivator (CIITA) (Jenkins et al., J. Virol, 2008).
In this study, we explored the impact of cmvIL-10 and hIL-10 on MHC Class I (MHC I) expression by CD14+ monocytes. We included examination of NLRC5, a cellular protein which has recently been reported to play an important role in transactivation of MHC I genes. Whilst cmvIL-10 and hIL-10 did not significantly alter surface expression of MHC I by freshly isolated CD14+ monocytes, transcription of NLRC5 and a range of genes associated with the MHC I antigen presentation pathway (HLA-A, HLA-B, B2M and LMP2) were significantly downregulated. These data indicate that cmvIL-10 may not rapidly alter constitutively expressed cell-surface MHC I, but may rather impair newly synthesized MHC I. To address this, we used LPS to stimulate surface MHC I by CD14+ monocytes in the presence of either cmvIL-10 or hIL-10. This analysis revealed inhibition of upregulation of surface MHC I protein as well as inhibited transcription of NLRC5 and MHC I associated genes. These results demonstrate that cmvIL-10 can impair the MHC I biosynthesis pathway, including a key regulator of this pathway, NLRC5. These findings provide evidence of an additional mechanism by which HCMV may restrict immune recognition and virus clearance.