Localization of human recombinant adenoviral vectors to the mitochondria following transduction of human cell lines.

Abstract

Recently, mitochondria have been shown to have a vital role in the innate immune response to viral infection. In response, viruses such as adenovirus, have developed mechanisms to alter mitochondrial function through direct or indirect interaction with the mitochondria. The interaction of human recombinant adenoviral vectors directly with human mitochondria has not previously been shown. We demonstrate that human recombinant adenoviral vectors co-localize to mitochondria. We show that the adenoviral vectors are present within the membranes of the mitochondria and that they cause ultrastructural changes to the cristae. Further, we show that the adenoviral genome is also present in intact mitochondria. We have posited that the interaction between the adenovirus and the mitochondria may act to inhibit mitochondrial function. We have also posited that the transport of the adenoviral genome to the mitochondria may allow the future use of this vector as a tool for gene therapy of mitochondrial diseases. Keywords: mitochondria; human recombinant adenovirus; gene therapy; viral vectors; mitochondrial DNA; electron microscopy.