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Human cytomegalovirus (HCMV) is a significant source of morbidity in neonates and the immunosuppressed that contains many genes that modulate antiviral signaling, yet how these genes contribute to shaping the host cell\u2019s transcriptional response to infection is largely unclear. Our results indicate that the HCMV U\n            <jats:sub>L<\/jats:sub>\n            26 protein is critical in preventing the establishment of a broad cellular proinflammatory transcriptional environment. Further, we find that the host gene IKK\u03b2 is an essential determinant governing the host cell\u2019s antiviral transcriptional response. 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