scholarly journals Human Cytomegalovirus Infection Suppresses CD34+ Progenitor Cell Engraftment in Humanized Mice

2020 ◽  
Vol 8 (4) ◽  
pp. 525
Author(s):  
Lindsey B. Crawford ◽  
Rebecca Tempel ◽  
Daniel N. Streblow ◽  
Andrew D. Yurochko ◽  
Felicia D. Goodrum ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Cytomegalovirus ◽  
Hematopoietic Cell Transplantation ◽  
Hcmv Infection ◽  
Treatment Strategies ◽  
Lymphoid Tissues ◽  
Cell Transplant ◽  
Humanized Mouse Model ◽  
Hematopoietic Stem ◽  
Cell Engraftment

Human cytomegalovirus (HCMV) infection is a serious complication in hematopoietic stem cell transplant (HSCT) recipients due to virus-induced myelosuppression and impairment of stem cell engraftment. Despite the clear clinical link between myelosuppression and HCMV infection, little is known about the mechanism(s) by which the virus inhibits normal hematopoiesis because of the strict species specificity and the lack of surrogate animal models. In this study, we developed a novel humanized mouse model system that recapitulates the HCMV-mediated engraftment failure after hematopoietic cell transplantation. We observed significant alterations in the hematopoietic populations in peripheral lymphoid tissues following engraftment of a subset of HCMV+ CD34+ hematopoietic progenitor cells (HPCs) within the transplant, suggesting that a small proportion of HCMV-infected CD34+ HPCs can profoundly affect HPC differentiation in the bone marrow microenvironment. This model will be instrumental to gain insight into the fundamental mechanisms of HCMV myelosuppression after HSCT and provides a platform to assess novel treatment strategies.

scholarly journals Human Cytomegalovirus Infection Suppresses CD34+ Progenitor Cell Engraftment in Humanized Mice

2020 ◽  
Author(s):  
Lindsey B. Crawford ◽  
Rebecca Tempel ◽  
Daniel N. Streblow ◽  
Andrew D. Yurochko ◽  
Felicia D. Goodrum ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Cytomegalovirus ◽  
Hematopoietic Cell Transplantation ◽  
Hcmv Infection ◽  
Treatment Strategies ◽  
Lymphoid Tissues ◽  
Cell Transplant ◽  
Humanized Mouse Model ◽  
Hematopoietic Stem ◽  
Cell Engraftment

Human Cytomegalovirus (HCMV) infection is a serious complication in hematopoietic stem cell transplant (HSCT) recipients due to virus-induced myelosuppression and impairment of stem cell engraftment. Despite the clear clinical link between myelosuppression and HCMV infection, little is known about the mechanism(s) by which the virus inhibits normal hematopoiesis because of the strict species specificity and the lack of surrogate animal models. In this study, we developed a novel humanized mouse model system that recapitulates the HCMV-mediated engraftment failure after hematopoietic cell transplantation. We observed significant alterations in the hematopoietic populations in peripheral lymphoid tissues following engraftment of a subset of HCMV+ CD34+ HPCs within the transplant suggesting that a small proportion of HCMV-infected CD34+ HPCs can profoundly affect HPC differentiation in the bone marrow microenvironment. This model will be instrumental to gain insight into the fundamental mechanisms of HCMV myelosuppression after HSCT and provides a platform to assess novel treatment strategies.

Human cytomegalovirus immediate-early mRNAemia versus pp65 antigenemia for guiding pre-emptive therapy in children and young adults undergoing hematopoietic stem cell transplantation: a prospective, randomized, open-label trial

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 5053-5060 ◽  
Author(s):  
Giuseppe Gerna ◽  
Daniele Lilleri ◽  
Fausto Baldanti ◽  
Maria Torsellini ◽  
Giovanna Giorgiani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
Immediate Early ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Hcmv Disease ◽  
Significant Difference

AbstractIn the search for better protocols of preemptive therapy of human cytomegalovirus (HCMV) infection in hematopoietic stem cell transplant (HSCT) recipients, we conducted a randomized trial comparing antigenemia with the nucleic acid sequence–based assay (NASBA) for determination of HCMV immediate-early messenger RNA (IEmRNA) as the guiding assay for initiation of pre-emptive antiviral treatment. In the IEmRNA arm, antiviral therapy was started upon IEmRNA positivity confirmed the following day, whereas in the antigenemia arm, therapy was started in the presence of either at least 2 pp65-positive leukocytes/2 × 105 examined or a single positive leukocyte confirmed the following day. In both arms, treatment was stopped upon 2 consecutive negative results. All patients were monitored for 3 months after HSCT. The primary end point of the study was duration of anti-HCMV therapy. On the whole, 80 children (41 in the IEmRNA and 39 in the antigenemia arm), recipients of transplants from either a relative or an unrelated donor, completed the study. No patient developed HCMV disease. In the IEmRNA arm, the incidence of HCMV infection was higher compared to the antigenemia arm (80% vs 51%, respectively, P = .0069), as well as the percentage of treated patients (66% vs 44%, respectively, P = .045). However, the percentage of relapses and treated relapses was comparable in the 2 arms. There was no significant difference in median duration of therapy per patient. Although these data indicate that IEmRNA determination does not offer advantages in terms of treatment duration, it can safely replace antigenemia, while semiautomation is the major advantage of the NASBA procedure.

Prospective simultaneous quantification of human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in young recipients of allogeneic hematopoietic stem cell transplants

Blood ◽  
2006 ◽  
Vol 108 (4) ◽  
pp. 1406-1412 ◽  
Author(s):  
Daniele Lilleri ◽  
Giuseppe Gerna ◽  
Chiara Fornara ◽  
Laura Lozza ◽  
Rita Maccario ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell ◽  
Human Cytomegalovirus ◽  
Immune Reconstitution ◽  
Hcmv Infection ◽  
Cd8 T Cell ◽  
Cell Transplant ◽  
Hematopoietic Stem

AbstractWe investigated immune reconstitution against human cytomegalovirus (HCMV) in 57 hematopoietic stem cell transplant (HSCT) recipients, aged 1 to 24 years, through a novel method combining T-cell stimulation by HCMV-infected autologous dendritic cells with simultaneous cytometric quantification of HCMV-specific, IFNγ-producing CD4+ and CD8+ T cells. Lymphoproliferative response (LPR) to HCMV antigens was also determined. Patients were stratified into 2 groups according to HCMV serostatus, comprising 39 HCMV-seropositive (R+) and 18 HCMV-seronegative (R–) patients who received a transplant from a sero-positive donor. Recovery of both HCMV-specific CD4+ and CD8+ T-cell immunity occurred in all 39 R+ patients within 6 months and in 6 (33%) of 18 R– patients within 12 months. In R+ patients, the median numbers of HCMV-specific CD8+ and CD4+T cells were significantly higher than those of healthy controls, starting from days +60 and +180, respectively. In R– patients, the median numbers of HCMV-specific T cells were consistently lower than in R+ patients. LPR was delayed compared with reconstitution of IFNγ-producing T cells. Patients with delayed specific immune reconstitution experienced recurrent episodes of HCMV infection. HCMV seropositivity of young HSCT recipients is the major factor responsible for HCMV-specific immune reconstitution, irrespective of donor serostatus, and measurement of HCMV-specific T cells appears useful for correct management of HCMV infection.

scholarly journals Natural Killer Cells Improve Hematopoietic Stem Cell Engraftment by Increasing Stem Cell Clonogenicity In Vitro and in a Humanized Mouse Model

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0138623 ◽  
Author(s):  
Michelle Escobedo-Cousin ◽  
Nicola Jackson ◽  
Raquel Laza-Briviesca ◽  
Linda Ariza-McNaughton ◽  
Martha Luevano ◽  
...  
Keyword(s):  
Stem Cell ◽  
Natural Killer Cells ◽  
Mouse Model ◽  
Natural Killer ◽  
Hematopoietic Stem Cell ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Hematopoietic Stem ◽  
Cell Engraftment
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