We discovered that neuropilin 1 (NRP1) is a new receptor candidate to mediate enterovirus A71 (EVA71) into cells. In the engineered form as a decoy receptor, NRP1 was able to recognize and neutralize EVA71 but not enterovirus D68 or coxsackievirus B3 (CVB3). NRP1 recognizes EVA71 through a novel domain on the VP3 capsid protein. The principle in the design, engineering, and refinement of the NRP1-based decoy receptor described in this study represents a general and well-suited antiviral strategy.
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http://dx.doi.org/10.1128/AAC.00695-20 | DOI Listing |
J Infect Chemother
January 2025
Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan; Department of Hematology, Oncology and Respiratory medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Enterovirus A71 (EV-A71) is a major pathogen responsible for hand, foot, and mouth disease (HFMD) in infants and children. EV-A71 infection represents an epidemic in the Asia-Pacific region, and can cause serious central nervous system (CNS) infections in immunocompromised patients that can result in paralysis, disability, or death. There have been few reports in the literature concerning EV-A71 CNS infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult patients.
View Article and Find Full Text PDFViruses
January 2025
Clinical Center for Biotherapy, Zhongshan Hospital, Fudan University, Shanghai 200433, China.
This study aimed to create a new recombinant virus by modifying the EV-A71 capsid protein, serving as a useful tool and model for studying human Enteroviruses. We developed a new screening method using EV-A71 pseudovirus particles to systematically identify suitable insertion sites and tag types in the VP1 capsid protein. The pseudovirus's infectivity and replication can be assessed by measuring postinfection luciferase signals.
View Article and Find Full Text PDFAntiviral Res
January 2025
CAMS Key Laboratory of Antiviral Drug Research, Beijing Key Laboratory of Technology and Application for Anti-Infective New Drugs Research and Development, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address:
Our previous study had found that cellular pseudokinase tribbles 3 (TRIB3) facilitates the infection of enterovirus A71 (EV-A71) via upregulating the protein level of EV-A71 receptor scavenger receptor class B member 2 (SCARB2). In the present study, we used metformin, which had been reported to down-regulate TRIB3 expression, to verify the potential of TRIB3 as an antiviral target. Here, we found that metformin can indeed impede the replication of EV-A71 and Coxsackievirus A16 (CVA16) through inhibiting the transcription of TRIB3 to indirectly down-regulate SCARB2 protein levels to block viral infection.
View Article and Find Full Text PDFmBio
January 2025
Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
Unlabelled: The KREMEN1 (KRM1) protein is a cellular receptor for multiple enteroviruses that cause hand, foot, and mouth disease (HFMD), including coxsackievirus CVA2, CVA3, CVA4, CVA5, CVA6, CVA10, and CVA12. The molecular basis for the broad recognition of these viruses by the KRM1 receptor remains unclear. Here, we report the indispensable role of the completely conserved VP2 capsid protein residue K140 (designated K2140) in mediating receptor recognition and infection by CVA10 and other KRM1-dependent enteroviruses.
View Article and Find Full Text PDFPathology
December 2024
Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Viral infections of the central nervous system (CNS) have been emerging and re-emerging worldwide, and the Australasia region has not been spared. Enterovirus A71 and enterovirus D68, both human enteroviruses, are likely to replace the soon-to-be eradicated poliovirus to cause global outbreaks associated with neurological disease. Although prevalent elsewhere, the newly emergent orthoflavivirus, Japanese encephalitis virus (genotype IV), caused human infections in Australia in 2021, and almost certainly will continue to do so because of spillovers from the natural animal host-vector life cycle endemic in the country.
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