Human adenoviruses (HAdVs) are the etiologic agent of many human infectious diseases. The existence of at least 54 different serotypes of HAdVs has resulted in difficulties in clinical diagnosis. Acute respiratory tract disease (ARD) caused by some serotypes from B and C species is particularly serious. Hexon, the main coat protein of HAdV, contains the major serotype-specific B cell epitopes; however, few studies have addressed epitope mapping in most HAdV serotypes. In this study, we utilized a novel and rapid method for the modeling of homologous proteins based on the phylogenetic tree of protein families and built three-dimensional (3D) models of hexon proteins in B and C species HAdVs. Based on refined hexon structures, we used reverse evolutionary trace (RET) bioinformatics analysis combined with a specially designed hexon epitope screening algorithm to achieve high-throughput epitope mapping of all 13 hexon proteins in B and C species HAdVs. This study has demonstrated that all of the epitopes from the 13 hexon proteins are located in the proteins' tower regions; however, the exact number, location, and size of the epitopes differ among the HAdV serotypes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0032938 | PLOS |
Theranostics
January 2025
Department of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
Adenovirus-based therapies have encountered significant challenges due to host immunity, particularly from pre-existing antibodies. Many trials have struggled to evade antibody response; however, the efficiency of these efforts was limited by the diversity of antibody Fv-region recognizing multiple amino acid sequences. In this study, we developed an antibody-evading adenovirus vector by encoding a plasma-rich protein transferrin-binding domain.
View Article and Find Full Text PDFViruses
November 2024
Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Certain species D human adenoviruses (HAdV-D19, -D37, and -D64) are causative agents of epidemic keratoconjunctivitis. HAdV-D37 has previously been shown to bind CD46 (membrane cofactor protein) and sialic acid as adhesion receptors. HAdV-D64 is genetically highly similar to HAdV-D37, with an identical fiber protein sequence, but differs substantially in its penton base and hexon proteins, two other major capsid components, due to genetic recombination.
View Article and Find Full Text PDFMol Ther Oncol
December 2024
Department of Gene Therapy, Ulm University, 89081 Ulm, Germany.
Respir Res
December 2024
Department of Respiratory Medicine Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, 400014, China.
Background: HAdV-7 is a prevalent pathogen that can cause severe pneumonia in children. Previous studies have shown a significant increase in serum levels of vascular permeability factor (VPF/VEGF) and viral load in pediatric patients with fatal HAdV-7 infection, suggesting potential damage to the pulmonary vascular endothelium. Further research is necessary to elucidate the underlying mechanism.
View Article and Find Full Text PDFVirol J
November 2024
Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.
Background: Human adenovirus type 7 (HAdV7) has become a major public health threat due to its widespread transmission, severe associated pneumonia, and a lack of effective anti-HAdV7 drugs. The aim of the current study is to design a humanized monoclonal antibody (mAb) demonstrating efficacy against HAdV-7 infections in vitro and in vivo.
Methods: The humanized neutralizing antibody, 3G5-hu, was derived from the murine mAb 3G5.
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