Nuclear import of HPV11 L1 capsid protein is mediated by karyopherin α2β1 heterodimers
✍ Scribed by Eric Merle; Robert C. Rose; Lucia LeRoux; Junona Moroianu
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 208 KB
- Volume
- 74
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
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 oligomeric configurations: as homopentameric capsomers, and as capsids composed of 72 capsomers. We found that intact L1 capsids of HPV type 11 cannot enter the nucleus, suggesting that capsid disassembly may be required for HPV11 L1 nuclear import. We established that HPV11 L1 is imported in a receptor-mediated manner into the nuclei of digitonin-permeabilized HeLa cells. HPV11 L1 docked at the nuclear pore complexes via karyopherin ␣21 heterodimers. Anti-karyopherin-1 and anti-karyopherin ␣2 antibodies specifically inhibited nuclear import of HPV11 L1. Moreover, nuclear import of HPV11 L1 could be reconstituted using karyopherin ␣2, 1, RanGDP and p10. In agreement with the docking and import data, we found that HPV11 L1 binds to karyopherin ␣2 and that this interaction is inhibited by a peptide representing the classical nuclear localization signal of SV40 T antigen. These results strongly suggest that HPV11 L1 enters the nucleus of the infected host cell via the karyopherin ␣21 pathway.