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The role of human cytomegalovirus in haematological diseases
1Clinical Research Centre, Royal Brisbane Hospital Foundation, Bancroft Centre, Queensland, Australia.
Abstract:
Infection with HCMV in healthy individuals generally results in mild or subclinical illness. Pathogenic infections occur predominantly in immunodeficient patients, such as transplant recipients, neonates and patients with AIDS. Primary infection is frequently latent or chronic and PBLs represent sites for virus latency and persistence. HCMV can be recovered from PMNL, monocytes and T-lymphocytes. Although virus-related cases of haematopoietic dysfunction are seen infrequently in infected normal persons, the importance of HCMV as a pathogenic agent in haematopoiesis is dramatically illustrated in the case of patients receiving BMT. Primary or reactivated HCMV infections are a common feature in BMT recipients, enhancing failure of marrow engraftment, GVHD, and many opportunistic infections. HCMV can infect both haematopoietic progenitor cells and stromal elements, identifying the entire haematopoietic system as a target for HCMV dissemination and latency. As a result, lympho- and myelosuppression can be due to both direct inhibition of progenitor cell growth as well as the failure of stem cell self-renewal due to stromal cell dysfunction. HCMV can also exert suppressive effects on immune cell function by direct and indirect mechanisms. These effects can have dire consequences, particularly when a state of immunosuppression already exists, as in the HIV infection. The diverse effects of CMV on the lymphohaematopoietic system are summarized in Figure 1.
Insights
Human Cytomegalovirus (HCMV) infection can cause severe illness in immunocompromised individuals, particularly bone marrow transplant (BMT) recipients. HCMV significantly impacts the lympho-hematopoietic system, leading to complications like graft failure and immune suppression.
Area of Science:
- Virology
- Immunology
- Hematology
Background:
- Healthy individuals typically experience mild Human Cytomegalovirus (HCMV) infections.
- Pathogenic HCMV infections predominantly affect immunocompromised patients, including transplant recipients, neonates, and individuals with AIDS.
- Peripheral blood lymphocytes (PBLs) are key sites for HCMV latency and persistence.
Purpose of the Study:
- To elucidate the pathogenic role of HCMV in the lympho-hematopoietic system.
- To understand HCMV's impact on hematopoiesis, particularly in bone marrow transplant (BMT) recipients.
- To summarize the diverse effects of HCMV on immune cell function.
Main Methods:
- Review and synthesis of existing literature on HCMV infection and its effects on the hematopoietic system.
- Analysis of HCMV's interaction with hematopoietic progenitor cells and stromal elements.
- Examination of direct and indirect mechanisms of immune cell suppression by HCMV.
Main Results:
- HCMV infection in BMT recipients is associated with marrow engraftment failure, graft-versus-host disease (GVHD), and opportunistic infections.
- HCMV infects both hematopoietic progenitor cells and stromal cells, targeting the entire hematopoietic system for dissemination and latency.
- HCMV-induced lympho- and myelosuppression result from direct progenitor cell inhibition and stromal cell dysfunction, impairing stem cell self-renewal.
Conclusions:
- HCMV poses a significant threat to the lympho-hematopoietic system, especially in immunocompromised states like HIV infection.
- The virus can suppress immune cell function through various mechanisms, exacerbating existing immunosuppression.
- Understanding HCMV's multifaceted effects is crucial for managing complications in vulnerable patient populations.