Human cytomegalovirus UL24 and UL43 products participate in SAMHD1 subcellular localization.

This report has analyzed the potential role of Human Cytomegalovirus (HCMV) UL24 and UL43 products in modulating the subcellular location of a host restriction factor, SAMHD1, in cells of human fibroblast origin. Recent studies have reported that the regulation of SAMHD1 is mediated by the HCMV UL97 product inside the nucleus, and by the CDK pathway when it is located in the cytoplasm of the infected cells but the viral gene products that may involve in cytosolic relocalization remain unknown yet. In the present report, we demonstrate that the HCMV UL24 product interacts with the SAMHD1 protein during infection based on mass spectrometry (MS) data and immunoprecipitation assay. The expression or depletion of the viral UL24 gene product did not affect the subcellular localization of SAMHD1 but when it coexpressed with the viral UL43 gene product, another member of the HCMV US22 family, induced the SAMHD1 cytosolic relocalization. Interestingly, the double deletion of viral UL24 and UL43 gene products impaired the cytosolic translocation and the SAMHD1 was accumulated in the nucleus of the infected cells, especially at the late stage post-infection. Our results provide evidence that the viral UL24 and UL43 gene products play a role in the SAMHD1 subcellular localization during HCMV infection. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-022-00799-3.