Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells.

Recombinant Adeno-Associated Virus (rAAV) is considered as one of the most successful and widely used viral vectors for in vivo gene therapy. However, host immune responses to the vector and/or the transgene product remain a major hurdle to successful AAV gene transfer. In contrast to antivector adaptive immunity, the initiation of the innate immunity towards rAAV is still poorly understood but is directly dependent on the interaction between the viral vector and innate immune cells. Here, we used a quantitative transcriptomic-based approach to determine the activation of inflammatory and anti-viral pathways after rAAV8-based infection of monocyte-derived dendritic cells (moDCs) obtained from 12 healthy human donors. We have shown that rAAV8 particles are efficiently internalized, but that this uptake does not induce any detectable transcriptomic change in moDCs in contrast to an adenoviral infection, which upregulates anti-viral pathways. These findings suggest an immunologically favorable profile for rAAV8 serotype with regard to in vitro activation of moDC model. Transcriptomic analysis of rAAV-infected innate immune cells is a powerful method to determine the ability of the viral vector to be seen by these sensor cells, which remains of great importance to better understand the immunogenicity of rAAV vectors and to design immune-stealth products.

Roles of LncRNAs in Viral Infections.

Many proteins and signaling pathways participate in anti-viral host responses. Long non-coding RNAs (lncRNAs), a subset of non-coding RNAs greater than 200 nucleotides in length, have been recently described as critical regulators in viral infections. Accumulating research indicates that lncRNAs are important in the development and progression of infectious diseases. LncRNAs are not only involved in anti-viral responses, but in many different virus-host interactions, some of which may be beneficial to the virus. Here we review the current knowledge regarding host and viral lncRNAs and their roles in viral infections. In addition, the potential of using lncRNAs as diagnostic biomarkers is discussed.