I am MSc graduate of medical virology from Ahvaz jundishapur university of medical science, Iran and currently working as a research assistant at Urmia university of medical science. We are doing some research on CMV infection in kidney transplant recipients, and I came across an unanswered question about the reactivation of CMV. Why do only a portion of seropositive transplant recipients develop CMV infection after transplantation?
I will appreciate it if you could help me find answer to my question.
Best regards
This is a complicated story, with multiple factors, but I will list here the most obvious reasons why only in some patients the virus reactivates:
1. Immune status - if the organ recipient was seropositive, with high antibody titers and large populations of CMV-specific cells prior to the transplantation (s)he may have sufficient residual immunity even after immune suppression to control the virus.
2. CMV load - if the patient is seropositive, but the latent viral load is low, the suppressed immune system may be sufficient to keep the virus in check.
3. CMV and host genetic polymorphism - some hosts may be better controllers than others due to HLAs that display CMV genes that are better displayed on the cell surface. Likewise, CMV strains differ and some of them might be more prone to reactivation.
4. Overall host status - there are reports that CMV reactivated in astronauts preparing for flights into space and that this was likely a result of elevated adrenalin. Similarly, the role of metabolism is recognized increasingly as an important determinant of viral replication and fitness. Differences in such factors are hence also likely to play a role.
Hope this helps
Luka
The immunosuppressive regimen post transplantation is an important factor as well, isn't it? CMV-specific CD8 and CD4 T-cell-counts may decrease due to the immunosuppressants.
Actually, there's an ongoing debate about mTOR-based regimens: they seem to have a CMV-protective character (e.g. by increasing the CMV-specific CD8 T-cell-count).
http://www.ncbi.nlm.nih.gov/pubmed/23269449
HI Davod
I'm agree in overall with Luka and Nici. There are many factores that attributed to reactivation rate of CMV in transplant patients and healthy cases too. These factors may be some to virus or more to host immune status.
The donor to recipient CMV serotype status as well as the use of induction agents (e.g. anti-thymocyte globulin vs. IL-2R antagonist), and the use of prophylactic vs. preemptive anti-CMV meds (i.e. valganciclovir) all affect the likelihood of CMV viremia/disease in the transplant recipients.
Try reading http://www.omicsonline.org/widespread-outbreaks-of-a-subtle-condition-leading-to-hospitalisation-and-death-2161-1165.1000137.php?aid=20306 as it gives a very broad background to some of the multiple complexities behind this enormously adaptable virus and its interaction with multiple immune impairments.
I have little to add to Luka Cicin-Sain's excellent response. A recipient's immune status may be compromised by the degree of immunosuppression, and one would expect the problem to occur with greater frequency in patients who undergo lymphocyte-depleting regimens..
Interesting article in Chinese Medical Journal 2012; 125(19): 3500-3504 for kidney transplantation. CMV was only a problem in those persons having the recessive alleleic gene Fok1 for vitamin D receptor.
Dear Davod,
In addition to the factors already mentioned by Dr. Luka, there is a direct relation to the type of immunosuppression that you will use in the receiver. We know that the induction Thymoglobulin provides a greater incidence of CMV infection when associated with immunosuppressive regimens with calcineurin inhibitors without the presence of mTOR inhibitors.
I compiled a few of the most interesting publications regarding to this matter: my focus is based on the role of immunosuppressants, especially the use of mTOR-inhibitors:
http://www.ncbi.nlm.nih.gov/pubmed/23269449,22541913,22390651,22574951,23222818,22683823,23146502,21787153,24088187,22320241,23876679,23311611,21040280,23165654,16386520
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