Cell infection by parvoviruses requires that capsids be delivered from outside the cell to the cytoplasm, followed by genome trafficking to the nucleus. Here we microinject capsids into cells that lack receptors and followed their movements within the cell over time. In general the capsids remained close to the positions where they were injected, and most particles did not move to the vicinity of or enter the nucleus. When 70 kDa-dextran was injected along with the capsids that did not enter the nucleus in significant amounts. Capsids conjugated to peptides containing the SV40 large T-antigen nuclear localization signal remained in the cytoplasm, although bovine serum albumen conjugated to the same peptide entered the nucleus rapidly. No effects of disruption of microfilaments, intermediate filaments, or microtubules on the distribution of the capsids were observed. These results suggest that movement of intact capsids within cells is primarily associated with passive processes.
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http://dx.doi.org/10.1016/j.virol.2014.04.003 | DOI Listing |
Nat Microbiol
January 2025
Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.
T cells have been identified as correlates of protection in viral infections. However, the level of vaccine-induced T cells needed and the extent to which they alone can control acute viral infection in humans remain uncertain. Here we conducted a double-blind, randomized controlled trial involving vaccination and challenge in 33 adult human volunteers, using the live-attenuated yellow fever (YF17D) and chimeric Japanese encephalitis-YF17D (JE/YF17D) vaccines.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Innovative Genomics Institute, University of California, Berkeley, CA 94720.
The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication proteins in EDVs has obscured the underlying delivery mechanism and precluded particle optimization.
View Article and Find Full Text PDFBiotechnol Lett
January 2025
Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Zhejiang Key Laboratory of Smart Biomaterials, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, China.
Objective: Adeno-associated viruses (AAVs) are widely used as gene therapy vectors due to their safety, stability, and long-term expression characteristics. The objective of this work is to develop an aqueous two-phase system (ATPS) as a universal platform for the separation and purification of AAVs.
Results: This study utilized polyethylene glycol (PEG)/salt ATPSs to separate and purify various AAV serotypes, including AAV5, AAV8, and AAV9, which focusing on serotype-specific performance and partial empty capsid removal.
Front Microbiol
December 2024
Infection Biology Laboratory, Instituto Superior de Investigaciones Biológicas (INSIBIO), CONI-CET-UNT, Tucumán, Argentina.
Introduction: The development of a hepatitis E virus (HEV) vaccine is critical, with ORF2 capsid protein as the main target. We previously demonstrated that oral coadministration of recombinant ORF2 with immunomodulatory bacterium-like-particles (IBLP) induces a specific immune response in mice, particularly using IBLP derived from IBL027 (IBLP027), which was effective in eliciting a local humoral response. IBLP are non-live bacteria with adjuvant and carrier properties, serving as a platform for exposing proteins or antigens fused to LysM (lysine motif) domains, protein modules that bind to cell wall polysaccharides like peptidoglycan.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Biochemistry, University of Colorado, Boulder, CO, United States of America.
PEG10 is a retroelement-derived Mart-family gene that is necessary for placentation and has been implicated in neurological disease. PEG10 resembles both retrotransposon and retroviral proteins and forms virus-like particles (VLPs) that can be purified using iodixanol ultracentrifugation. It is hypothesized that formation of VLPs is crucial to the biological roles of PEG10 in reproduction and neurological health.
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