title: Adenovirus transport via direct interaction of cytoplasmic dynein with the viral capsid hexon subunit.
abstract: Early in infection, adenovirus travels to the nucleus as a naked capsid using the microtubule motor cytoplasmic dynein. How the dynein complex is recruited to viral cargo remains unclear. We find that cytoplasmic dynein and its associated proteins dynactin and NudE/NudEL, but not LIS1 or ZW10, colocalized with incoming, postendosomal adenovirus particles. However, in contrast to physiological cargos, dynein binding to adenovirus was independent of these dynein-associated proteins. Dynein itself directly interacted through its intermediate and light intermediate chains with the adenovirus capsid subunit hexon in a pH-dependent manner. Expression of hexon or injection of anti-hexon antibody inhibited virus transport but not physiological dynein function. These results identify hexon as a direct receptor for cytoplasmic dynein and demonstrate that hexon recruits dynein for transport to the nucleus by a mechanism distinct from that for physiological dynein cargo.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: K Helen
authors.initials: KH
authors.lastname: Bremner
authors.forename: Julian
authors.initials: J
authors.lastname: Scherer
authors.forename: Julie
authors.initials: J
authors.lastname: Yi
authors.forename: Michael
authors.initials: M
authors.lastname: Vershinin
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gross
authors.forename: Richard B
authors.initials: RB
authors.lastname: Vallee
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D000257:Adenoviridae Infections / Q000378:metabolism / Q000821:virology*; D000818:Animals; D001692:Biological Transport; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D056445:Cytoplasmic Dyneins / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding
chemical_list: D036022:Capsid Proteins; C018315:hexon capsid protein, Adenovirus; D056445:Cytoplasmic Dyneins