Mechanisms of human cytomegalovirus (HCMV) (re)activation and its impact on organ transplant patients.
Human cytomegalovirus (HCMV) infection plays an important role in transplant patients. Its impact is both direct and indirect. This review focuses on new aspects of HCMV (re)activation and HCMV related pathology, particularly HCMV-associated renal allograft injury. During the last two years we have learned that HCMV is more frequently (re)activated, even in healthy people, than previously expected. Inflammatory as well as stress mediators and some drugs may (re)activate the virus by using distinct intracellular pathways. Commonly, HCMV (re)activation is accompanied by HCMV antigenemia/DNAemia, suggesting that precursor cells in the bone marrow play an important role as a reservoir of latent virus. However, local HCMV (re)activation (colon, lung) without detection of active HCMV infection in the peripheral blood is possible. In healthy people a sufficient type 1 T-cell response controls the active HCMV infection, while in patients with severe immune deficiency (AIDS, high-dose immunosuppression) the virus can spread in an uncontrolled fashion and induce 'classic' HCMV disease. In patients with moderate immune deficiency (e.g. long-term transplant patients on low-dose immunosuppression) virus spreading is controlled but the elimination of cells harboring the active virus may be insufficient. The resulting persistent HCMV antigenemia may induce chronic inflammatory processes leading to tissue injury, particularly in the allograft. Therefore, antiviral therapy may be useful in patients suffering from graft deterioration with otherwise clinically symptomless HCMV infection. HCMV-related immune deficiency with an increased risk of developing bacterial/fungal superinfections is frequently seen in patients with symptomatic HCMV disease but not in asymptomatic CMV antigenemia. The risk of developing superinfections can be predicted by flow-cytometric monitoring of peripheral blood monocytes.
Reinke
P
P
Department of Nephrology and Internal Intensive Care, Charité--Campus Virchow, Humboldt-University Berlin, Berlin, Germany.
Prösch
S
S
Kern
F
F
Volk
H D
HD
D015415:Biomarkers / Q000097:blood; D003587:Cytomegalovirus / Q000254:growth & development*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000503:physiopathology* / Q000517:prevention & control; D006684:HLA-DR Antigens / Q000097:blood; D006801:Humans; D016377:Organ Transplantation; D011183:Postoperative Complications; D012008:Recurrence; D014775:Virus Activation / Q000502:physiology*
D015415:Biomarkers; D006684:HLA-DR Antigens