Evaluation of Two Different CMV-Immunoglobulin Regimens for Combined CMV Prophylaxis in High-Risk Patients following Lung Transplant

Cuesta, Víctor Manuel Mora; Ussetti, Piedad; Pablo, Alicia de; Iturbe-Fernández, David; Laporta, Rosalía; Alonso, Raquel Cano; Aguilar, Myriam; Quezada, Carlos; Cifrián, José

doi:10.3390/microorganisms11010032

Cited by 2 publications

(1 citation statement)

References 48 publications

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“…99 A recent observational study of 124 D+/R− lung transplant recipients receiving (val)ganciclovir prophylaxis compared short- (n = 62) versus extended-course (n = 62) CMV immunoglobulin in the prevention of CMV infection. 100 They found no difference between groups with respective CMV infection, acute rejection, chronic allograft dysfunction, or survival 1-y posttransplantation.…”

Section: Management Of CMV Infectionmentioning

confidence: 93%

What’s New: Updates on Cytomegalovirus in Solid Organ Transplantation

Stewart,

Kotton

2023

Transplantation

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Cytomegalovirus (CMV) is one of the most common infections occurring after solid organ transplantation. This high burden of disease, which incurs sizeable morbidity, may be worsening with the proportion of high-risk D+/R− solid organ transplantation recipients increasing in some regions globally. Cohort studies continue to support either universal prophylaxis or preemptive therapy as effective prevention strategies. Letermovir prophylaxis was noninferior to valganciclovir in adult high-risk D+/R− kidney transplant recipients with fewer drug-related adverse events in a recent clinical trial and has now been approved for such use in some regions. Maribavir preemptive therapy failed to demonstrate noninferiority when compared with valganciclovir in hematopoietic stem cell transplant recipients but looked promising for safety. Donor matching could be useful in prevention CMV disease with a survival advantage demonstrated in seronegative recipients waiting up to 30 mo for a seronegative kidney. Immune-guided prophylaxis resulted in fewer CMV infection episodes in lung transplant recipients when compared with fixed-duration prophylaxis in a recent clinical trial. For treatment of refractory or resistant CMV infection, maribavir was more efficacious and better tolerated when compared with investigator-initiated therapy in its registration trial for this condition. Further research regarding best treatment and prophylaxis of resistant or refractory CMV infection is needed to reflect best clinical practice choices. Optimal use of immune globulin or CMV-specific T cells for prevention or treatment of CMV disease remains undefined. Standardized definitions for the design of CMV clinical trials have been developed. In this review, we highlight recent updates in the field from data published since 2018.

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Section: Management Of CMV Infectionmentioning

confidence: 93%

What’s New: Updates on Cytomegalovirus in Solid Organ Transplantation

Stewart,

Kotton

2023

Transplantation

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Understanding the Cytomegalovirus Cyclin-Dependent Kinase Ortholog pUL97 as a Multifaceted Regulator and an Antiviral Drug Target

Marschall,

Schütz,

Wild

et al. 2024

Cells

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Herpesviral protein kinases, such as the therapy-relevant pUL97 of human cytomegalovirus (HCMV), are important for viral replication efficiency as well as pathogenesis, and represent key antiviral drug targets. HCMV pUL97 is a viral cyclin-dependent kinase (CDK) ortholog, as it shares functional and structural properties with human CDKs. Recently, the formation of vCDK/pUL97–cyclin complexes and the phosphorylation of a variety of viral and cellular substrate proteins has been demonstrated. Genetic mapping and structural modeling approaches helped to define two pUL97 interfaces, IF1 and IF2, responsible for cyclin binding. In particular, the regulatory importance of interactions between vCDK/pUL97 and host cyclins as well as CDKs has been highlighted, both as determinants of virus replication and as a novel drug-targeting option. This aspect was substantiated by the finding that virus replication was impaired upon cyclin type H knock-down, and that such host-directed interference also affected viruses resistant to existing therapies. Beyond the formation of binary interactive complexes, a ternary pUL97–cyclin H–CDK7 complex has also been described, and in light of this, an experimental trans-stimulation of CDK7 activity by pUL97 appeared crucial for virus–host coregulation. In accordance with this understanding, several novel antiviral targeting options have emerged. These include kinase inhibitors directed to pUL97, to host CDKs, and to the pUL97–cyclin H interactive complexes. Importantly, a statistically significant drug synergy has recently been reported for antiviral treatment schemes using combinations of pharmacologically relevant CDK7 and vCDK/pUL97 inhibitors, including maribavir. Combined, such findings provide increased options for anti-HCMV control. This review focuses on regulatory interactions of vCDK/pUL97 with the host cyclin–CDK apparatus, and it addresses the functional relevance of these key effector complexes for viral replication and pathogenesis. On this basis, novel strategies of antiviral drug targeting are defined.

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Evaluation of Two Different CMV-Immunoglobulin Regimens for Combined CMV Prophylaxis in High-Risk Patients following Lung Transplant

Cited by 2 publications

References 48 publications

What’s New: Updates on Cytomegalovirus in Solid Organ Transplantation

What’s New: Updates on Cytomegalovirus in Solid Organ Transplantation

Understanding the Cytomegalovirus Cyclin-Dependent Kinase Ortholog pUL97 as a Multifaceted Regulator and an Antiviral Drug Target

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