Down-regulation of single-stranded DNA-binding protein 1 expression induced by HCMV infection promotes lipid accumulation in cells

Abstract

The objective of this study was to observe the infection of human cytomegalovirus (HCMV) to human umbilical vein endothelial cells, and its effect on the expression of single-stranded DNA-binding protein (SSBP1) and on lipid metabolism in endothelial cells. We screened the differential expression of mRNAs after HCMV infection by suppression subtractive hybridization and the expression levels of SSBP1 mRNA and protein after HCMV infection by real-time PCR and western blot. After verification of successful infection by indirect immunofluorescent staining and RT-PCR, we found a differential expression of lipid metabolism-related genes including LDLR, SCARB, CETP, HMGCR, ApoB and LPL induced by HCMV infection. The expression levels of SSBP1 mRNA and protein after HCMV infection were significantly down-regulated. Furthermore, we found that upregulation of SSBP1 inhibited the expression of atherosclerosis-associated LDLR, SCARB, HMGCR, CETP as well as the accumulation of lipids in the cells. The results showed that the inhibition of SSBP1 by HCMV infection promotes lipid accumulation in the cells.

Human cytomegalovirus infection and coronary heart disease: a systematic review

“…A recent study showed that upregulation of single-stranded DNA-binding protein-1 (SSBP1) inhibits the expression of AS-associated low-density lipoprotein receptor, scavenger receptor class B, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and cholesteryl ester transfer protein, along with the accumulation of lipids in cells. The inhibition of SSBP1 by HCMV infection promotes this lipid accumulation [ 114 ], which depends on the uptake of OX-LDL, a process in which the scavenger receptor (SR) has been postulated to play an important role. Zhou et al demonstrated that HCMV infection of human SMCs increases modified LDL uptake and stimulates the expression of class A SR gene mRNA [ 115 ].…”

Interplay between Lipid Metabolism, Lipid Droplets, and DNA Virus Infections

“…High levels of GLUT4 expression increase glucose import, as well as nuclear translocation of the glucose-regulated transcription factor carbohydrate-responsive element-binding protein (ChREBP), which ultimately induces the transcription of genes encoding lipogenic enzymes, resulting in a rise in lipid synthesis, LD accumulation, and viral envelope generation [ 157 ]. Moreover, HCMV induces the expression of low-density lipoprotein receptor (LDLR), scavenger receptor class B (SCARB), cholesteryl ester transfer protein (CETP), HMGCR, apolipoprotein B (ApoB), and LPL in human umbilical vein endothelial cells [ 158 ]. On the other hand, the accumulation of LDs has also been reported in fibroblasts infected with murine CMV (mCMV) [ 159 ].…”

The Role of CMV Infection in Primary Lesions, Development and Clinical Expression of Atherosclerosis

“…The homology of pUS28 to HSP60 can also determine smooth muscle cells' migration within vascular intima [55]. In vitro, CMV infects vascular smooth muscle cells, resulting in important alterations in the expression of lipid metabolism genes with intracellular cholesterol accumulation [56], possibly by downregulation of SSBP1, which is an important protein involved in wound repair [57].…”