The role of receptors in the maturation-dependent adenoviral transduction of myofibers

One of the major hurdles facing the application of adenoviral gene transfer to skeletal muscle is the maturation-dependent transduction of muscle myof ibers, it was recently proposed that the viral receptors (Coxsackie and ade novirus receptor (CAR) and the integrins alphav beta3/beta5) play a major r ole in the poor adenoviral transduction of mature myofibers. Here we report the findings of morphological studies designed to determine experimentally the role of receptors in the adenoviral transduction of mature myofibers. First, we observed that the expression of both attachment and internalizati on receptors did not change significantly during muscle development. Second , when an extended tropism adenoviral vector (AdPK) that attaches to hepara n sulfate proteoglycan (HSP) is used, a significant reduction of adenoviral transduction still occurs in mature myofibers despite HSP's high expressio n in mature skeletal muscle fibers. Third, when the adeno-associated virus (AAV) is used, which also utilizes HSP as a viral receptor, muscle fibers a t different maturities can be highly transduced Fourth, the pre-irradiation of the skeletal muscle of newborn mice to inactivate myoblasts dramaticall y decreased the transduction level of Ad and AdPK, but had no effect on AAV -mediated viral transduction of immature myofibers. These results taken tog ether suggest that the viral receptor(s) is not a major determinant in matu ration-dependent adenoviral transduction of myofibers.