Cytoplasmic parvovirus capsids recruit importin beta for nuclear delivery

Abstract

Parvoviruses are an important platform for gene and cancer therapy. Their cell entry and the following steps including nuclear import are inefficient limiting their use in therapeutic applications. Two models exist on parvoviral nuclear entry: classical import of the viral capsid using nuclear transport receptors of the importin (karyopherin) family, or direct attachment of the capsid to the nuclear pore complex leading to local disintegration of the nuclear envelope. Here, by laser scanning confocal microscopy and in situ proximity ligation analysis combined with co-immunoprecipitation we showed that infection requires importin β-mediated access into the nuclear pore complex and nucleoporin 153-mediated interactions on the nuclear side. Importin β-capsid interaction continued within the nucleoplasm, which suggests that a mixed model of nuclear entry in which the classical nuclear import across the nuclear pore complex is accompanied by transient ruptures of the nuclear envelope allowing also passive entry of importin β-capsid complexes into the nucleus.