Abstract
SAMHD1 is a newly identified anti-HIV host factor that has a dNTP triphosphohydrolase activity and depletes intracellular dNTP pools in non-dividing myeloid cells. Since DNA viruses utilize cellular dNTPs, we investigated whether SAMHD1 limits the replication of DNA viruses in non-dividing myeloid target cells. Indeed, two double stranded DNA viruses, vaccinia and herpes simplex virus type 1, are subject to SAMHD1 restriction in non-dividing target cells in a dNTP dependent manner. Using a thymidine kinase deficient strain of vaccinia virus, we demonstrate a greater restriction of viral replication in non-dividing cells expressing SAMHD1. Therefore, this study suggests that SAMHD1 is a potential innate anti-viral player that suppresses the replication of a wide range of DNA viruses, as well as retroviruses, which infect non-dividing myeloid cells.
Highlights
It is becoming increasingly evident that host cells employ metabolic regulatory mechanisms in order to restrict the life cycle of pathogens [1,2,3,4]
A series of recent studies revealed that the host protein SAMHD1 is deoxynucleoside triphosphates (dNTPs) triphosphohydrolase, which contributes to the poor dNTP abundance in non-dividing myeloid cells, and restricts proviral DNA synthesis of HIV-1 and other lentiviruses in macrophages, dendritic cells, and resting T cells
We demonstrate that SAMHD1 controls the replication of large double stranded DNA (dsDNA) viruses: vaccinia virus and HSV1, in primary human monocyte-derived macrophages
Summary
It is becoming increasingly evident that host cells employ metabolic regulatory mechanisms in order to restrict the life cycle of pathogens [1,2,3,4]. SAMHD1 is a dNTPs triphosphohydrolase, and functions by hydrolyzing dNTPs into dNs and triphosphates [9,10], leading to the reduction of cellular dNTP concentrations [5,6]. This in turn can impact the kinetics of cellular, viral, and parasitic DNA polymerization by reducing the availability of dNTP substrate for the enzyme. We previously reported that terminally differentiated/non-dividing monocyte-derived macrophages (MDMs), which are a HIV target cell type [13], have 22–320 times lower dNTP concentrations compared to actively dividing
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