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Development of RT-PCR Assays for Simple Detection and Identification of Sabin Virus Contaminants in the Novel Oral Poliovirus Vaccines.
Vaccines (Basel)
January 2025
Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA.
Background/objectives: Conventional live oral poliovirus vaccines (OPVs) effectively prevent poliomyelitis. These vaccines are derived from three attenuated Sabin strains of poliovirus, which can revert within the first week of replication to a neurovirulent phenotype, leading to sporadic cases of vaccine-associated paralytic poliomyelitis (VAPP) among vaccinees and their contacts. A novel OPV2 vaccine (nOPV2) with enhanced genetic stability was developed recently; type 1 and type 3 nOPV strains were engineered using the nOPV2 genome as a backbone by replacing the capsid precursor polyprotein (P1) with that of Sabin strains type 1 and type 3, respectively.
View Article and Find Full Text PDFMolecular basis for shifted receptor recognition by an encephalitic arbovirus.
bioRxiv
January 2025
Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
After decades of inactivity throughout the Americas, western equine encephalitis virus (WEEV) recently re-emerged in South America, causing a large-scale outbreak in humans and horses. WEEV binds protocadherin 10 (PCDH10) as a receptor; however, nonpathogenic strains no longer bind human or equine PCDH10 but retain the ability to bind avian receptors. Highly virulent WEEV strains can also bind the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as alternative receptors.
View Article and Find Full Text PDFNeurovirulent Pathogens Across the Human Lifespan: A Balancing Act.
J Pediatric Infect Dis Soc
January 2025
Division of Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Key virulence factors responsible for differences in pathogenicity between clinically proven live-attenuated Japanese encephalitis vaccine SA14-14-2 and its pre-attenuated highly virulent parent SA14.
PLoS Pathog
January 2025
Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, Utah, United States of America.
Japanese encephalitis virus (JEV), a neuroinvasive and neurovirulent orthoflavivirus, can be prevented in humans with the SA14-14-2 vaccine, a live-attenuated version derived from the wild-type SA14 strain. To determine the viral factors responsible for the differences in pathogenicity between SA14 and SA14-14-2, we initially established a reverse genetics system that includes a pair of full-length infectious cDNAs for both strains. Using this cDNA pair, we then systematically exchanged genomic regions between SA14 and SA14-14-2 to generate 20 chimeric viruses and evaluated their replication capability in cell culture and their pathogenic potential in mice.
View Article and Find Full Text PDFHeterogeneous Ribonucleoprotein K Is a Host Regulatory Factor of Chikungunya Virus Replication in Astrocytes.
Viruses
December 2024
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Chikungunya virus (CHIKV) is an emerging, mosquito-borne arthritic alphavirus increasingly associated with severe neurological sequelae and long-term morbidity. However, there is limited understanding of the crucial host components involved in CHIKV replicase assembly complex formation, and thus virus replication and virulence-determining factors, within the central nervous system (CNS). Furthermore, the majority of CHIKV CNS studies focus on neuronal infection, even though astrocytes represent the main cerebral target.
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