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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,2,8]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Previous proteomic analyses of host factors targeted for down-regulation by human cytomegalovirus (HCMV) have focused on early or intermediate stages of infection. Using multiplexed proteomics, we have systematically identified viral factors that target each host protein down-regulated during the latest stage of infection, after the onset of viral DNA replication. Schlafen-11 (SLFN11), an interferon-stimulated gene and restriction factor for retroviruses and certain RNA viruses, potently restricted HCMV infection. Our discovery that the late-expressed HCMV protein RL1 targets SLFN11 for proteasomal degradation provides evidence for a viral antagonist of this critical cellular protein. 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