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Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting
Published on: October 26, 2018
A common mechanism for cytoplasmic dynein-dependent microtubule binding shared among adeno-associated virus and
Samir Kelkar1, Bishnu P De, Guangping Gao
1Department of Genetic Medicine, Weill Medical College of Cornell University, 515 E. 71st Street, S-1000, New York, NY 10021, USA. geneticmedicine@med.cornell.edu
Abstract:
During infection, adenovirus-associated virus (AAV) undergoes microtubule-dependent retrograde transport as part of a program of vectorial transport of viral genome to the nucleus. A microtubule binding assay was used to evaluate the hypothesis that cytoplasmic dynein mediates AAV interaction with microtubules. Binding of AAV serotype 2 (AAV2) was enhanced in a nucleotide-dependent manner by the presence of total cellular microtubule-associated proteins (MAPs) but not cytoplasmic dynein-depleted MAPs. Excess AAV2 capsid protein prevented microtubule binding by AAV serotypes 2, 5, and rh.10, as well as adenovirus serotype 5, indicating that similar binding sites are used by these viruses.
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