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ss of valosin-containing protein (VCP/p97), which promotes the expression of viral major immediate-early gene products, in a manner dependent on its membrane targeting, but a small isoform of pUL50 is expressed to negatively regulate this pUL50 activity. This study reports a new NEC-independent function of pUL50 and highlights the fine regulation of pUL50 activity by a smaller isoform for efficient viral growth. Copyright © 2020 American Society for Microbiology.It is widely held that clinical isolates of human cytomegalovirus (HCMV) ar