Cyclosporine Versus Tacrolimus: Which Calcineurin Inhibitor Has Influence on Cytomegalovirus Infection in Cardiac Transplantation?

Bond, Marina Macedo Kuenzer; Bond, Marisa Macedo Kuenzer; Sehn, Ana Paula; Dias, V.H.; Said, Tarek; Santos, Carolina Casadei Dos; Finger, Marco Aurélio; Santos, Ângela; Neto, João Manoel Rossi

doi:10.1016/j.transproceed.2018.02.046

Cited by 7 publications

(5 citation statements)

References 17 publications

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“…KEYWORDS CD63, ESCRTs, GW4869, HCMV, extracellular vesicles, spread H uman cytomegalovirus (HCMV) is a leading cause of congenital viral infection, which can result in numerous complications for the developing fetus and newborn. Infection of immunocompromised individuals is also a significant source of disease, particularly in solid organ and hematopoietic cell transplant recipients, where virus infection is commonly detected in patients (1)(2)(3). There is a need to understand the molecular mechanisms of infection to provide new therapeutic targets to combat antiviral resistance and toxicity associated with the currently approved therapies.…”

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confidence: 99%

Human Cytomegalovirus Utilizes Extracellular Vesicles To Enhance Virus Spread

Streck

Zhao

Sundstrom

et al. 2020

J Virol

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Human cytomegalovirus (HCMV) manipulates cellular processes associated with secretory pathways within an infected cell to facilitate efficient viral replication. However, little is known about how HCMV infection alters the surrounding cellular environment to promote virus spread to uninfected cells. Extracellular vesicles (EVs) are key signaling molecules that are commonly altered in numerous disease states. Previous reports have shown that viruses commonly alter EVs, which can significantly impact infection. This study finds that HCMV modulates EV biogenesis machinery through upregulation of the endosomal sorting complex required for transport (ESCRT) proteins. This regulation appears to increase the activity of EV biogenesis, since HCMV-infected fibroblasts have increased vesicle release and altered vesicle size compared to EVs from uninfected cells. EVs generated through ESCRT-independent pathways are also beneficial to virus spread in fibroblasts, as treatment with the EV inhibitor GW4869 slowed the efficiency of HCMV spread. Importantly, the transfer of EVs purified from HCMV-infected cells enhanced virus spread. This suggests that HCMV modulates the EV pathway to transfer proviral signals to uninfected cells that prime the cellular environment for incoming infection and enhance the efficiency of virus spread. IMPORTANCE Human cytomegalovirus (HCMV) is a herpesvirus that leads to serious health consequences in neonatal or immunocompromised patients. Clinical management of infection in these at-risk groups remains a serious concern even with approved antiviral therapies available. It is necessary to increase our understanding of the cellular changes that occur during infection and their importance to virus spread. This may help to identify new targets during infection that will lead to the development of novel treatment strategies. Extracellular vesicles (EVs) represent an important method of intercellular communication in the human host. This study finds that HCMV manipulates this pathway to increase the efficiency of virus spread to uninfected cells. This finding defines a new layer of host manipulation induced by HCMV infection that leads to enhanced virus spread.

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confidence: 99%

Human Cytomegalovirus Utilizes Extracellular Vesicles To Enhance Virus Spread

Streck

Zhao

Sundstrom

et al. 2020

J Virol

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“…We found that cyclosporine was associated with more risk for CMV infection, but this could be due to a bigger number of patients taking tacrolimus (n = 239, 91.9%) than cyclosporine (n = 21, 8.1%). However, there is a Brazilian heart transplantation case-control study [27] with similar results: they found out that positive PCR correlated with higher doses of a CNI in a statistically significant way (p = 0.002), as did an elevated serum level of cyclosporine (p = 0.004) whereas elevated serum levels of tacrolimus had no such association (p = 0.17).…”

Section: Discussionmentioning

confidence: 58%

A Retrospective Review of Calcineurin Inhibitors’ Impact on Cytomegalovirus Infections in Lung Transplant Recipients

et al. 2021

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Immunosuppressive therapy reduces the risk for allograft rejection but leaves recipients susceptible to infections. Cytomegalovirus (CMV) is one of the most frequent causes for infection after transplantation and increases the risk for allograft rejection. As lung transplant recipients (LTRs) need to be under immunosuppression for life, they are a vulnerable group. To determine the potential association between the development of CMV infection and the calcineurin inhibitor (CNI) blood levels within previous 90 days, a retrospective review of LTRs was performed. Data from recipients who underwent a lung transplantation (LTx) at our center from January 2011 to December 2018 were collected. The studied recipients, after case/control matching, included 128 CMV-infection cases. The median time from the transplant to the first positive CMV viral load was 291.5 days. In our study, more patients were treated with tacrolimus (91.9%) than with cyclosporine (8.1%). Drug blood levels at selected timepoints showed no statistically significant difference between cases and controls. However, we found that CMV infection was more frequent in the donor-seropositive/recipient-seronegative group, interstitial lung disease (ILD) recipients, LTRs who underwent basiliximab induction, cyclosporine treated recipients, and LTRs with lymphopenia (at the time of CMV infection and 90 days before). In this review of LTRs, no association between the CNI blood level and CMV infection was seen, although other immunity-related factors were found to be influencing, i.e., basiliximab induction, cyclosporine treatment, and lymphopenia.

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“…Like induction immunosuppression, maintenance immunosuppressive regimens have also been associated with the risk of CMV infection and disease. Most of our literature cases report a maintenance immunosuppression regimen of cyclosporine, azathioprine, and steroids; cyclosporine may be associated with higher rates of CMV infection when compared to tacrolimus, another calcineurin inhibitor, including in heart transplant recipients 23,24 . In our patients, one was on a regimen of tacrolimus, MMF, and prednisone and the other a regimen of belatacept, MMF, and prednisone.…”

Section: Discussionmentioning

confidence: 76%

Cytomegalovirus myocarditis in solid organ transplant recipients: A case series and review of literature

Scherger

Mathur

Bajrovic

et al. 2020

Transplant Infectious Dis

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Cytomegalovirus (CMV) is a DNA virus of the Herpesviridae family and is estimated to affect 15%-30% of high-risk solid organ transplant recipients. Typical manifestations of CMV end-organ disease in this population include colitis, esophagitis, and pneumonitis, and myocarditis is a rarely reported manifestation. We describe two cases of CMV myocarditis in solid organ transplant recipients and review the literature regarding previously published cases of CMV myocarditis. K E Y W O R D S cytomegalovirus, solid organ transplant recipients How to cite this article: Scherger S, Mathur S, Bajrovic V, et al. Cytomegalovirus myocarditis in solid organ transplant recipients: A case series and review of literature. Transpl Infect

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Cyclosporine Versus Tacrolimus: Which Calcineurin Inhibitor Has Influence on Cytomegalovirus Infection in Cardiac Transplantation?

Cited by 7 publications

References 17 publications

Human Cytomegalovirus Utilizes Extracellular Vesicles To Enhance Virus Spread

Human Cytomegalovirus Utilizes Extracellular Vesicles To Enhance Virus Spread

A Retrospective Review of Calcineurin Inhibitors’ Impact on Cytomegalovirus Infections in Lung Transplant Recipients

Cytomegalovirus myocarditis in solid organ transplant recipients: A case series and review of literature

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