We describe studies of woodchuck hepatitis virus nucleic acids in liver and other tissues of chronically infected woodchucks, using Southern and Northern blot hybridization techniques. Single-stranded and covalently closed circular replicative DNA molecules were distinguished from partly double-stranded virus genomes. In most animals the liver contained more virus than any other organ, but all extrahepatic organs studied (spleen, thymus, pancreas, and kidney) contained viral DNA and significant amounts of viral RNA. In the spleen, partly double-stranded virus genomes were present at higher levels than in any other organ but liver, but nonetheless replicative intermediates were not detected. The observation of RNA transcripts in the absence of detectable covalently closed circular DNA template suggests that a small proportion of cells in extrahepatic tissues are infected with WHV.
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http://dx.doi.org/10.1016/0042-6822(89)90035-4 | DOI Listing |
Genome Res
November 2024
Research Data Science Group, R&D, CSL, Parkville, Victoria 3000, Australia.
J Virol
August 2024
Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
Unlabelled: Many viruses have evolved structured RNA elements that can influence transcript abundance and translational efficiency, and help evade host immune factors by hijacking cellular machinery during replication. Here, we evaluated the functional impact of sub-genomic flaviviral RNAs (sfRNAs) known to stall exoribonuclease activity, by incorporating these elements into recombinant adeno-associated viral (AAV) genome cassettes. Specifically, sfRNAs from Dengue, Zika, Japanese Encephalitis, Yellow Fever, Murray Valley Encephalitis, and West Nile viruses increased transcript stability and transgene expression compared to a conventional woodchuck hepatitis virus element (WPRE).
View Article and Find Full Text PDFHum Gene Ther
August 2024
Biogen Inc., Cambridge, Massachusetts, USA.
Choroideremia, an incurable, progressive retinal degeneration primarily affecting young men, leads to sight loss. GEMINI was a multicenter, open-label, prospective, two-period, interventional Phase II study assessing the safety of bilateral sequential administration of timrepigene emparvovec, a gene therapy, in adult males with genetically confirmed choroideremia (NCT03507686, ClinicalTrials.gov).
View Article and Find Full Text PDFHum Gene Ther
September 2024
Takeda Pharmaceuticals USA, Inc., Cambridge, Massachusetts, USA.
Fabry disease (FD) is a multisystemic lysosomal storage disorder caused by the loss of α-galactosidase A (α-Gal) function. The current standard of care, enzyme replacement therapies, while effective in reducing kidney pathology when treated early, do not fully ameliorate cardiac issues, neuropathic manifestations, and risk of cerebrovascular events. Adeno-associated virus (AAV)-based gene therapies (AAV-GT) can provide superior efficacy across multiple tissues owing to continuous, endogenous production of the therapeutic enzyme and lower treatment burden.
View Article and Find Full Text PDFViruses
May 2024
Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
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