Human cytomegalovirus (HCMV) is the leading viral cause of birth defects and organ transplant rejection. The HCMV gH/gL/UL128/UL130/UL131A complex (Pentamer) is the main target of humoral responses and thus a key vaccine candidate. We report two structures of Pentamer bound to human neutralizing antibodies, 8I21 and 9I6, at 3.0 and 5.9 Å resolution, respectively. The HCMV gH/gL architecture is similar to that of Epstein-Barr virus (EBV) except for amino-terminal extensions on both subunits. The extension of gL forms a subdomain composed of a three-helix bundle and a β hairpin that acts as a docking site for UL128/UL130/UL131A. Structural analysis reveals that Pentamer is a flexible molecule, and suggests sites for engineering stabilizing mutations. We also identify immunogenic surfaces important for cellular interactions by epitope mapping and functional assays. These results can guide the development of effective vaccines and immunotherapeutics against HCMV.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1126/sciimmunol.aan1457 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Study on mechanism of Spatholobi Caulis in the treatment of the hand-foot skin reaction induced by targeted drug therapy based on network pharmacology and molecular docking: An observational study.
Medicine (Baltimore)
January 2025
Department of Traditional Chinese Medicine, Shanghai Fourth People's Hospital Affiliated to Tongji University of Medicine, Shanghai, China.
Based on network pharmacology and molecular docking methods, this study explored its active compounds and confirmed its potential mechanism of action against Hand-foot skin reaction induced by tumor-targeted drugs. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and UniProt Database were used to obtain the active ingredients and target proteins of Spatholobi Caulis. All hand-foot skin reaction (HFSR)-related targets were obtained with the help of the Human Gene Database, Online Mendelian Inheritance in Humans (OMIM), DisGeNET and DrugBank databases.
View Article and Find Full Text PDFEnhanced Costimulation Blockade With αCD154, αCD2, and αCD28 to Promote Heart Allograft Tolerance in Nonhuman Primates.
Transplantation
January 2025
Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Background: Long-term renal allograft acceptance has been achieved in macaques using a transient mixed hematopoetic chimerism protocol, but similar regimens have proven unsuccessful in heart allograft recipients unless a kidney transplant was performed simultaneously. Here, we test whether a modified protocol based on targeting CD154, CD2, and CD28 is sufficient to prolong heart allograft acceptance or promote the expansion of regulatory T cells.
Methods: Eight macaques underwent heterotopic allo-heart transplantation from major histocompatibility complex-mismatched donors.
Demographic Features, Diagnoses and Real-World Clinical Management of Uveitis in Japan.
Ocul Immunol Inflamm
January 2025
Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan.
Purpose: This study aimed to investigate demographic features, diagnoses of uveitis (intraocular inflammation), and real-world clinical practice in the use of local and systemic therapies for patients with uveitis in Tokyo, Japan.
Methods: Clinical records of 1,174 consecutive new patients (480 males, 694 females) referred to the Kyorin Eye Center, Kyorin University Hospital between January 2011 and December 2018 were retrospectively reviewed.
Results: Mean age at presentation was 52.
Diagnostic Performance of Two Different Techniques to Quantify CMV-Specific Cell-Mediated Immunity in Intermediate-Risk Seropositive Kidney Transplant Recipients.
Transpl Infect Dis
January 2025
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.
Background: Kidney transplant (KT) recipients at intermediate risk for cytomegalovirus (CMV) infection constitute a potential target for individualized prevention strategies informed by the CMV-specific cell-mediated immunity (CMV-CMI). The optimal method for the functional assessment of CMV-CMI in this group remains unclear.
Methods: We included 74 CMV-seropositive KT recipients that did not receive T-cell-depleting induction and were managed by preemptive therapy.
Persisting Gaps in Cytomegalovirus Prevention and Management After Solid Organ Transplantation in a Resource-Limited Setting.
Transpl Infect Dis
January 2025
Department of Infectious Diseases, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil.
Background: Cytomegalovirus (CMV) infection remains among the leading complications after solid organ transplantation (SOT). Large international surveys mainly focused on high-income countries, detected considerable variability in the management of this infection after SOT. Limited data are available from resource-limited settings.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!