Human cytomegalovirus tropism for endothelial cells: not all endothelial cells are created equal.

Abstract

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that persists for the life of the host following initial infection. Genome analysis indicates that mammalian CMVs have cospeciated with their respective host over the last 80 million years (39). This prolonged period of coevolution has resulted in a high level of coadaptation between virus and host. The study of CMV, a virus that is exquisitely adapted for persistence within the host, is beginning to reveal strategies critical for virus survival. Although all herpesviruses persist for the life span of the host, recent findings suggest that HCMV has a unique replication strategy for maintenance within the host, wherein the virus establishes sites of persistent active replication even in the presence of high levels of preexisting HCMV-specific immunity. A number of cell types, including myeloid lineage cells, smooth muscle cells, and endothelial cells (ECs), appear to be critical as sites of HCMV persistent replication and latency. HCMV infections of myeloid lineage and of smooth muscle cells have been the focuses of previous reviews (see references 32 and 66). This review will focus on HCMV infection of ECs and the role of this cell type in virus persistence and latency. We will describe a “genomic island” of three genes that are essential for HCMV EC tropism and discuss mechanisms by which the products of these genes mediate HCMV infection in ECs.