Reactivation of human cytomegalovirus in dendritic cells.
Extract: Human cytomegalovirus (HCMV) is a member of the Herpesvirus family of viruses and is a ubiquitous human pathogen. Primary infection of immunocompetent individuals is rarely problematic, but congenital or neonatal infection, or infection in immunosuppressed individuals, can cause severe disease. An important biological characteristic of HCMV, with obvious clinical importance, is the ability of the virus to establish lifelong persistence in the host following the initial, normally asymptomatic, infection. A key strategy used by all herpesviruses to persist in the infected individual is the establishment of cellular sites of viral latency. Viral latency is operationally defined as the persistence of the viral genome in absence of the production of infectious virions, but with the ability of the viral genome to reactivate under certain conditions. HCMV can remain latent in peripheral blood cells throughout the host's lifetime and sporadic reactivation events are generally well controlled by cell-mediated immunosurveillance, particularly virus-specific CD4+ and CD8+ T lymphocytes. However, in immunocompromised AIDS patients or immunosuppressed transplant patients, HCMV replication becomes uncontrolled and can cause serious morbidity and mortality, due to disease in the eye (retinitis), lung, nervous system and other organs. Analyses of virus strains during HCMV infection of organ transplant patients have shown that infection is predominantly due to reactivation of the transplant recipient's own HCMV, although it can also result from virus transferred from the donor. Consequently, an understanding of the cellular sites of latency and reactivation, and the mechanisms that control latency in these cells, are of major importance for further understanding of HCMV pathogenesis, as it follows reactivation.
Reeves
Matthew
M
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK.
Sissons
Patrick
P
Sinclair
John
J