Hepatitis D virus interferes with hepatitis B virus RNA production via interferon-dependent and -independent mechanisms.

Background & Aims: Chronic coinfection with HBV and HDV leads to the most aggressive form of chronic viral hepatitis. Herein, we aimed to elucidate the molecular mechanisms underlying the widely reported observation that HDV interferes with HBV in most coinfected patients.

Methods: Patient liver tissues, primary human hepatocytes, HepaRG cells and human liver chimeric mice were used to analyze the effect of HDV on HBV using virological and RNA-sequencing analyses, as well as RNA synthesis, stability and association assays.

AAV capsid engineering identified two novel variants with improved in vivo tropism for cardiomyocytes.

AAV vectors are promising delivery tools for human gene therapy. However, broad tissue tropism and pre-existing immunity against natural serotypes limit their clinical use. We identified two AAV capsid variants, AAV2-THGTPAD and AAV2-NLPGSGD, by in vivo AAV2 peptide display library screening in a murine model of pressure overload-induced cardiac hypertrophy.

Novel AAV capsids for intravitreal gene therapy of photoreceptor disorders.

Gene therapy using recombinant adeno-associated virus (rAAV) vectors to treat blinding retinal dystrophies has become clinical reality. Therapeutically impactful targeting of photoreceptors still relies on subretinal vector delivery, which detaches the retina and harbours substantial risks of collateral damage, often without achieving widespread photoreceptor transduction. Herein, we report the development of novel engineered rAAV vectors that enable efficient targeting of photoreceptors via less invasive intravitreal administration.

Intrinsic Differential Scanning Fluorimetry for Fast and Easy Identification of Adeno-Associated Virus Serotypes.

Recombinant adeno-associated virus (AAV) vectors have evolved as the most promising technology for gene therapy due to their good safety profile, high transduction efficacy, and long-term gene expression in non-dividing cells. AAV-based gene therapy holds great promise for treating genetic disorders like inherited blindness, muscular atrophy, or bleeding disorders. Multiple naturally occurring and engineered AAV serotypes exist, which differ in capsid sequence and as a consequence in cellular tropism.

Vector uncoating limits adeno-associated viral vector-mediated transduction of human dendritic cells and vector immunogenicity.

AAV vectors poorly transduce Dendritic cells (DC), a feature invoked to explain AAV's low immunogenicity. However, the reason for this non-permissiveness remained elusive. Here, we performed an in-depth analysis using human monocyte-derived immature DC (iDC) as model.

Characterization of AAV vector particle stability at the single-capsid level.

Virus families have evolved different strategies for genome uncoating, which are also followed by recombinant vectors. Vectors derived from adeno-associated viruses (AAV) are considered as leading delivery tools for in vivo gene transfer, and in particular gene therapy. Using a combination of atomic force microscopy (AFM), biochemical experiments, and physical modeling, we investigated here the physical properties and stability of AAV vector particles.

Interference with the production of infectious viral particles and bimodal inhibition of replication are broadly conserved antiviral properties of IFITMs.

IFITMs are broad antiviral factors that block incoming virions in endosomal vesicles, protecting target cells from infection. In the case of HIV-1, we and others reported the existence of an additional antiviral mechanism through which IFITMs lead to the production of virions of reduced infectivity. However, whether this second mechanism of inhibition is unique to HIV or extends to other viruses is currently unknown.

[Integration of AAV vectors and insertional mutagenesis].

Recombinant AAV vectors (rAAV) are considered as very efficient tools for in vivo gene transfer. Accordingly, several preclinical and clinical gene therapy trials use these vectors to treat inherited and acquired diseases. rAAV vectors possess the capacity to persist for a long term in the transduced tissue in a transcriptionally active, extra-chromosomal (episomal) form.

Les vecteurs AAV pour le transfert de gène in vivo ou comment un petit virus devient grand.

Among the variety of viral vectors, those derived from the human parvovirus Adeno-Associated Virus (AAV) have emerged as a very efficient tool for in vivo gene transfer into a variety of tissues and animal species during the two last decades. The relative simplicity of the organization of the AAV genome and the non-pathogenic property of the parental AAV has greatly contributed to the use of this viral vector among the gene transfer community. However, the limited knowledge of the wild type (wt) virus compared to other viral vectors has required considerable efforts to gain insight into wt AAV biology in order to improve the AAV vector system for therapy.