HCMV: Molecular basis of persistence and latency

Human cytomegalovirus (HCMV) is an ubiquitous herpesvirus that establishes a lifelong infection within the host. Although HCMV is generally asymptomatic within the normal individual, the virus causes severe and incapacitating disease in immune compromised patients (Pass, 2001). A critical component for HCMV persistence in the non-immune compromised host is the ability of the virus to establish cellular sites of latency as well as persistent infection. During latency, the HCMV genome is maintained within the cell with limited viral gene expression reactivating virus upon cellular stimulation. In HCMV persistent infection, infectious virus is continually produced in the cell with minimal cytopathic effect thereby enabling long-term infection. Endothelial cells (ECs) and specific subpopulations of the myeloid lineage are believed to represent important sites of persistent HCMV replication and latency, respectively. Recent studies of HCMV and the closely related murine cytomegalovirus (MCMV) are beginning to identify the virally encoded genetic determinants required for replication in these cell types. The establishment of latent infection in myeloid cells that are critical cellular components of the host immune system, also closely interconnects HCMV and the host immune response. This chapter will focus on the role of ECs and myeloid cells as sites of CMV persistent replication and latency, and the viral mechanisms that modulate cellular functions to ensure survival and reactivation within the host.