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Exploitation of Unconventional CD8 T-Cell Responses Induced by Engineered Cytomegaloviruses for the Development of an HIV-1 Vaccine.
Vaccines (Basel)
January 2025
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK.
After four decades of intensive research, traditional vaccination strategies for HIV-1 remain ineffective due to HIV-1's extraordinary genetic diversity and complex immune evasion mechanisms. Cytomegaloviruses (CMV) have emerged as a novel type of vaccine vector with unique advantages due to CMV persistence and immunogenicity. Rhesus macaques vaccinated with molecular clone 68-1 of RhCMV (RhCMV68-1) engineered to express simian immunodeficiency virus (SIV) immunogens elicited an unconventional major histocompatibility complex class Ib allele E (MHC-E)-restricted CD8 T-cell response, which consistently protected over half of the animals against a highly pathogenic SIV challenge.
View Article and Find Full Text PDFHuman Cytomegalovirus Infection Induces Long-Term Changes in the Cytokine Milieu of Kidney Transplant Recipients.
J Med Virol
January 2025
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.
The impact of human cytomegalovirus (HCMV) infection on the mid- and long-term balance between pro-inflammatory and anti-inflammatory cytokines among kidney transplant recipients (KTRs) remains unclear. We measured plasma levels of 12 Th1/Th2-type cytokines (granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin [IL]-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-18 and tumor necrosis factor-α) in a cohort of 290 KTRs at four time points through month 12 after transplantation. Cytokine levels at each point were compared according to the previous documentation of HCMV replication by two approaches: "cumulative exposure" from the time of transplantation and "recent exposure" within the 2-3 months preceding cytokine assessment.
View Article and Find Full Text PDFComplex roles for proliferating cell nuclear antigen in restricting human cytomegalovirus replication.
bioRxiv
January 2025
Graduate Program in Molecular Medicine, University of Arizona, Tucson, Arizona, USA.
DNA viruses at once elicit and commandeer host pathways, including DNA repair pathways for virus replication. Despite encoding its own DNA polymerase and processivity factor, human cytomegalovirus (HCMV) recruits the cellular processivity factor, proliferating cell nuclear antigen (PCNA) and specialized host DNA polymerases involved in translesion synthesis (TLS) to replication compartments (RCs) where viral DNA (vDNA) is synthesized. While the recruitment of TLS polymerases is important for viral genome stability, the role of PCNA is poorly understood.
View Article and Find Full Text PDFThe UW Experience: Feasibility of De Novo Letermovir for Primary Prophylaxis After Abdominal Solid Organ Transplant.
Ann Pharmacother
January 2025
Department of Pharmacy, University of Wisconsin Hospital and Clinics, UW Health, Madison WI, USA.
Background: Letermovir is approved for primary prophylaxis of cytomegalovirus (CMV) in high-risk kidney transplant recipients. However, many experts suggest the drug be reserved as a second-line agent when valganciclovir is not tolerated or fails.
Objective: The purpose of this study was to describe the feasibility of a de novo letermovir prophylactic approach for CMV high-risk and seropositive abdominal solid organ transplant patients.
Transplantation of a genetically modified porcine heart into a live human.
Nat Med
January 2025
Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Following our previous experience with cardiac xenotransplantation of a genetically modified porcine heart into a live human, we sought to achieve improved results by selecting a healthier recipient and through more sensitive donor screening for potential zoonotic pathogens. Here we transplanted a 10-gene-edited pig heart into a 58-year-old man with progressive, debilitating inotrope-dependent heart failure due to ischemic cardiomyopathy who was not a candidate for standard advanced heart failure therapies. He was maintained on a costimulation (anti-CD40L, Tegoprubart) blockade-based immunomodulatory regimen.
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