Cytomegalovirus stimulated mRNA accumulation and cell surface expression of the oxidized LDL scavenger receptor, CD36.
OBJECTIVE
Cytomegalovirus (CMV) has been epidemiologically associated with multiple disease processes including coronary, carotid and cardiac graft atherosclerosis. An early initiating event in atherogenesis is the uptake by macrophages of oxidized low-density lipoproteins (OxLDL) via the scavenger receptor, CD36. Because CMV can activate host-cell gene transcription, we hypothesized that CMV may upregulate CD36 expression.


RESULTS
THP-1 monocyte/macrophage cells were treated with Davis strain CMV and cell surface CD36 expression measured by flow cytometry. Virus challenge increased the percentage of cells expressing CD36 from 21.8 +/- 1.7 to 48.2 +/- 4.0% (mean +/- S.D. for three experiments, P=0.0005); CD36 mRNA accumulation was increased by CMV treatment as determined by reverse transcription-polymerase chain reaction. Viral challenge also upregulated the mitogen-activated protein kinase p38; further, the specific p38 inhibitor, SB203580, reversed the CMV-induced CD36 cell surface expression from 57.2% of cells to baseline levels (29.0 and 30.1% for SB203580 treated and control cells, respectively; P=0.001). Treatment with virus also stimulated uptake of OxLDL: microscopically, virus-treated cells had a mean of 32 +/- 4.0 lipid vacuoles compared with 20 +/- 1.3 for control cells (P=0.01).


CONCLUSIONS
These findings suggest that CMV-induced CD36 expression is one mechanism through which CMV may promote atherosclerosis. Other CMV-associated atherogenic mechanisms may exist; additional investigation is necessary.
Cardiovascular Department, LDS Hospital, 8th Avenue and C Street, Salt Lake City, UT 84143, USA. john.carlquist@ihc.com
John F
JF
Carlquist
Joseph B
JB
Muhlestein
Benjamin D
BD
Horne
Noal I
NI
Hart
Tobin
T
Lim
Jessica
J
Habashi
Jeffrey G
JG
Anderson
Jeffrey L
JL
Anderson
D018955:CD36 Antigens; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000502:physiology*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics*; D051116:Receptors, Scavenger; D015854:Up-Regulation
D018955:CD36 Antigens; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger