The human cytomegalovirus (HCMV) envelope contains 12 virus-encoded glycoproteins and glycoprotein complexes but the lipid composition of the envelope has not been clearly defined. Given the specificity of the interactions between integral membrane proteins and lipids, it is likely that the lipid content of the virion envelope is regulated during infection. In an effort to determine the effects of HCMV infection on lipid metabolism, we have used PCR array technology to investigate how infection affects the expression of genes involved in lipoprotein signaling and cholesterol homeostasis pathways. Our results indicate that HCMV infection leads to down-regulation of the ABCA1 transporter. Decreased levels of ABCA1 appear to be the result of enhanced calpain-mediated cleavage in virus-infected cells. In addition, our data also show that HCMV infection inhibits the development of the foam cell phenotype in conditionally permissive THP-1 derived macrophages. © 2010 Elsevier Inc.