Progress and Challenges in the Prevention, Diagnosis, and Management of Cytomegalovirus Infection in Transplantation

Limaye, Ajit P.; Babu, Tara M; Boeckh, Michael

doi:10.1128/cmr.00043-19

Cited by 67 publications

(71 citation statements)

References 273 publications

(356 reference statements)

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“…CMV is currently a major health problem, in particular for patients with impaired cell-mediated immunity [2], such as solid organ transplant recipients, hematopoietic cell transplant recipients [3], HIVinfected patients [4], and patients treated with immunomodulating drugs [5]. For those immunocompromised patients, CMV infection or reactivation cause several morbidities, including gastrointestinal tract disease, pneumonia, hepatitis, and encephalitis, as well as increasing the chance of organ rejection and opportunistic infections [6]. Hence, CMV viral load monitoring is recommended.…”

Section: Introductionmentioning

confidence: 99%

Cytomegalovirus Viral Load in Transplanted Patients Using the NeuMoDx™ (Qiagen) Automated System: A 1-Month Experience Feedback

Luciani

Mongin

Ninove

et al. 2021

Viruses

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Cytomegalovirus (CMV) reactivations represent a significant morbidity and mortality problem in transplant patients. Reliable and rapid measurement of CMV viral load is a key issue for optimal patient management. We report here the evaluation of NeuMoDx™ (Qiagen) in a routine hospital setting (University Hospitals of Marseille, France) in comparison with our classical reference technique R-GENE. During one month, 719 CMV viral loads from 507 patients were measured in parallel in both techniques. Using the ROC (receiver operating characteristic) curve and our biological experience we suggest that values <52 IU/mL (geometric mean) correspond to negative samples, values >140 IU/mL (Fowlkes–Mallows index) correspond to quantifiable positive results and values ranging from 52 to 140 IU/mL represent non-quantifiable positive results. Follow-up of 15 transplant patients who developed CMV reactivation during the study showed that NeuMoDx™ provided higher viral load measurement during the first two weeks of follow-up for three patients. These important intra-individual variations resulted in a significant median increase considering the whole data set (6.7 points of difference expressed as a percentage of the initial viral load). However, no difference between the two techniques was noticeable after two weeks of treatment. Subsequent to this first study we conclude that NeuMoDx™, used with optimized logistics and an adapted threshold, allows a rapid CMV viral load measurement and that its use does not lead to any difference in patient management compared to the reference technique R-GENE®.

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Section: Introductionmentioning

confidence: 99%

Cytomegalovirus Viral Load in Transplanted Patients Using the NeuMoDx™ (Qiagen) Automated System: A 1-Month Experience Feedback

Luciani

Mongin

Ninove

et al. 2021

Viruses

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“…A few antiviral drugs, including ganciclovir and valganciclovir, have been used for treating CMV infection, but viral resistance is a major challenge associated with their use [ 1 ]. Another approach is the transfer of donor-derived CMV-specific CTLs, but it remains limited due to the occurrence of graft-versus-host disease (GVHD) in allogeneic recipients [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…Human cytomegalovirus (CMV), a β-herpes virus with a double-stranded DNA, infects a wide variety of cells and establishes latency in the host [ 1 ]. CMV infection is very common in adults (60‒90% of the population), with higher infection rates with age [ 2 ], and is usually asymptomatic in healthy subjects but can cause severe diseases in immunocompromised patients with cellular immunosuppression or immunodeficiency, including transplant recipients and fetuses [ 1 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Affinity Maturation of a T-Cell Receptor-Like Antibody Specific for a Cytomegalovirus pp65-Derived Peptide Presented by HLA-A*02:01

Lee

Son

et al. 2021

IJMS

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Human cytomegalovirus (CMV) infection is widespread among adults (60–90%) and is usually undetected in healthy individuals without symptoms but can cause severe diseases in immunocompromised hosts. T-cell receptor (TCR)-like antibodies (Abs), which recognize complex antigens (peptide–MHC complex, pMHC) composed of MHC molecules with embedded short peptides derived from intracellular proteins, including pathogenic viral proteins, can serve as diagnostic and/or therapeutic agents. In this study, we aimed to engineer a TCR-like Ab specific for pMHC comprising a CMV pp65 protein-derived peptide (495NLVPMVATV503; hereafter, CMVpp65495-503) in complex with MHC-I molecule human leukocyte antigen (HLA)-A*02:01 (CMVpp65495-503/HLA-A*02:01) to increase affinity by sequential mutagenesis of complementarity-determining regions using yeast surface display technology. Compared with the parental Ab, the final generated Ab (C1-17) showed ~67-fold enhanced binding affinity (KD ≈ 5.2 nM) for the soluble pMHC, thereby detecting the cell surface-displayed CMVpp65495-503/HLA-A*02:01 complex with high sensitivity and exquisite specificity. Thus, the new high-affinity TCR-like Ab may be used for the detection and treatment of CMV infection.

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“…Cytomegalovirus is a severe virus which causes deadly infections among immunosuppressed patients [42]. Human cytomegalovirus (HCMV) open reading frames (ORF) encodes four vGPCRs: US28, US27, UL33, and UL78; the first three mimic chemokine receptor structure.…”

Section: Cytomegalovirus (Cmv)mentioning

confidence: 99%

Methods for Studying Endocytotic Pathways of Herpesvirus Encoded G Protein-Coupled Receptors

et al. 2020

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Endocytosis is a fundamental process involved in trafficking of various extracellular and transmembrane molecules from the cell surface to its interior. This enables cells to communicate and respond to external environments, maintain cellular homeostasis, and transduce signals. G protein-coupled receptors (GPCRs) constitute a family of receptors with seven transmembrane alpha-helical domains (7TM receptors) expressed at the cell surface, where they regulate physiological and pathological cellular processes. Several herpesviruses encode receptors (vGPCRs) which benefits the virus by avoiding host immune surveillance, supporting viral dissemination, and thereby establishing widespread and lifelong infection, processes where receptor signaling and/or endocytosis seem central. vGPCRs are rising as potential drug targets as exemplified by the cytomegalovirus-encoded receptor US28, where its constitutive internalization has been exploited for selective drug delivery in virus infected cells. Therefore, studying GPCR trafficking is of great importance. This review provides an overview of the current knowledge of endocytic and cell localization properties of vGPCRs and methodological approaches used for studying receptor internalization. Using such novel approaches, we show constitutive internalization of the BILF1 receptor from human and porcine γ-1 herpesviruses and present motifs from the eukaryotic linear motif (ELM) resources with importance for vGPCR endocytosis.

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Progress and Challenges in the Prevention, Diagnosis, and Management of Cytomegalovirus Infection in Transplantation

Cited by 67 publications

References 273 publications

Cytomegalovirus Viral Load in Transplanted Patients Using the NeuMoDx™ (Qiagen) Automated System: A 1-Month Experience Feedback

Cytomegalovirus Viral Load in Transplanted Patients Using the NeuMoDx™ (Qiagen) Automated System: A 1-Month Experience Feedback

Affinity Maturation of a T-Cell Receptor-Like Antibody Specific for a Cytomegalovirus pp65-Derived Peptide Presented by HLA-A*02:01

Methods for Studying Endocytotic Pathways of Herpesvirus Encoded G Protein-Coupled Receptors

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