Nuclear import of HPV11 L1 capsid protein is mediated by karyopherin alpha2 beta 1 heterodimers

L1 major capsid proteins of human papillomaviruses (HPVs) enter the nuclei of host cells at two times during the viral life cycle: 1) after infection and 2) later during the productive phase, when they assemble the replicated HPV genomic DNA into infectious virions. L1 proteins are stable in two oli gomeric configurations: as homopentameric capsomers, and as capsids compose d of 72 capsomers. We found that intact L1 capsids of HPV type 11 cannot en ter the nucleus, suggesting that capsid disassembly may be required for HPV 11 L1 nuclear import. We established that HPV11 L1 is imported in a recepto r-mediated manner into the nuclei of digitonin-permeabilized HeLa cells. HP V11 L1 docked at the nuclear pore complexes via karyopherin alpha 2 beta 1 heterodimers. Anti-karyopherin-beta 1 and anti-karyopherin alpha 2 antibodi es specifically inhibited nuclear import of HPV11 L1. Moreover, nuclear imp ort of HPV11 L1 could be reconstituted using karyopherin alpha 2, beta 1, R anGDP and p10. In agreement with the docking and import data, we found that HPV11 L1 binds to karyopherin alpha 2 and that this interaction is inhibit ed by a peptide representing the classical nuclear localization signal of S V40 T antigen. These results strongly suggest that HPV11 L1 enters the nucl eus of the infected host cell via the karyopherin alpha 2 beta 1 pathway. ( C) 1999 Wiley-Liss, Inc.