| Summary: | Viruses have evolved many novel mechanisms to promote infection and to mitigate the host cell response to that infection. In the article by M. H. Hancock et al. (mBio 8:e00109-17, 2017, https://doi.org/10.1128/mBio.00109-17), the authors describe a new mechanism by which human cytomegalovirus (HCMV) microRNAs (miRNAs; miR-US5-1 and miR-UL112-3p) negate the proinflammatory response to infection. The authors document that these two viral miRNAs downregulate the NF-κB response through direct targeting of the IKKα and IKKβ mRNAs, which in turn, through diminished IκB kinases (IKKs), block production of proinflammatory cytokines (interleukin-6 [IL-6], CCL5, and tumor necrosis factor alpha [TNF-α]). Because most signaling pathways that promote NF-κB activation and nuclear translocation ultimately converge on the activation of the IKK complex, this new study documents that HCMV can strongly dictate how infected cells respond to internal and/or external stimuli and thus positively influence the outcome of both lytic and latent infection.
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