HCMV UL24 and UL43 Genes may Facilitate Immune Evasion through Viral miR-UL59 Regulation

Abstract UL24 and UL43 are two tegument proteins of the US22 family of Human Cytomegalovirus (HCMV). The role of these two proteins is poorly understood, especially in host cellular interaction. Using co-immunoprecipitation and protein-identification by mass spectrometry, we characterized some intracellular proteins that are complex with viral UL24 and UL43 proteins. We identified that these two viral proteins could interact with each other and also with host cellular proteins, Dicer, and TRBP, which are important cofactors to regulate the biogenesis of the cellular miRNAs. The knockout of these two genes has significantly crippled the expression of HCMV miR-UL59 in the infected cells. Besides, the depletion of these viral genes has increased the mRNA expression of the UL16 binding protein 1 (ULBP1), a target gene of miR-UL59, which is a cell surface glycoprotein present on Natural Killer (NK) cells and other immune cells. These data indicate that UL24 and UL43 proteins may affect the expression of ULBP1 by regulating miR-UL59 to prevent the recognition of infected cells by the immune cells and thus may facilitate HCMV immune evasion. This study provides some theoretical basis for the future development of RNA-targeted small molecules to control HCMV infection.