Abstract

Cytomegalovirus is one of the most immunodominant antigens that are encountered by the human immune system. The human cytomegalovirus (HCMV) exhibits a broad cellular tropism and can infect most major organ systems and cell types. Immunologic control of HCMV replication includes several distinct categories of effector cells: natural killer cells, macrophages, B cells and T cells however virus-specific CD8+ and CD4+ T cells appear to play a pivotal role. The importance of cell mediated immunity against CMV is exemplified by the occurrence of severe and prolonged HCMV infection in immunocompromised individuals, including transplant recipients, late stage -HIV patients, congenitally infected neonates, elderly subjects and/or septic patients. Severely impaired T-cell function leads to viral reactivation and consequences are widely variable, ranging from asymptomatic infections to life-threatening situations. Monitoring of protective HCMV-specific immune response may serve as an early predictive marker for identifying individuals at high risk for HCMV disease prior to the detection of increased viremia. The identification of patients who are at high risk of CMV is a more complex challenge for the laboratory. Mainly HCMV specific T cell immunity, resp. enumeration of CD8+ HCMV specific T cells would be expected to correlate with the incidence of HCMV disease. Recently, it has become possible to enumerate antigen-specific CD8+ T cells by using tetramers. HCMVspecific cellular immunity by evaluating the activation capacity of CD8+ T cells to a mitogenic stimulus or whole HCMV antigen or HCMV peptides assessed by IFNγ ELISPOT or ELISA seem to be promising in the assessment of HCMV specific function/immunity. However the clinical utility of these assays will need to be evaluated.

Highlights

  • Human cytomegalovirus (HCMV), a member of Herpesviridae family, is a ubiquitous opportunistic pathogen

  • HCMV genome contains a number of accessory genes; most of them are engaged in immune evasion or inhibition of cell death

  • The cellular target of HCMV infection remains incompletelly defined, the widespread expression of putative cell surface receptors including proteoglykans, integrins and epidermal grow factor receptor suggest that the tropism of virus is not limited to specific cell types on the mucosal surfaces

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Summary

Introduction

Human cytomegalovirus (HCMV), a member of Herpesviridae family, is a ubiquitous opportunistic pathogen. After an initial primary infection, HCMV can remain latent throughout the lifetime of the host and sporadic reactivation events, if they occur, are generally well controlled by immunosurveillance. The cellular target of HCMV infection remains incompletelly defined, the widespread expression of putative cell surface receptors including proteoglykans, integrins and epidermal grow factor receptor suggest that the tropism of virus is not limited to specific cell types on the mucosal surfaces. After mucosal infection with HCMV, local and initial viremia leads to infection of visceral structures such as the liver and spleen. Macrophages [9,10,11] It appeared that HCMV infection of host cells, including monocytes and endothelial cells, could induce expression of variety mediators of the inflammatory response including adhesion molecules, chemokines, cytokines, and pro-inflammatory enzymes such as COX-2 [6]. Infection of immunocompromised hosts, especially organ and stem cell transplantant recipients and AIDS patients can be devastating

Immune response to HCMV infection
HCMV infection in immunocompromised individuals
HCMV infection and primary immunodeficiences
HCMV in immunosuppressed patients
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