Nuclear import strategies of high risk HPV16 L1 major capsid protein.
During the late phase of human papillomavirus (HPV) infection, the L1 major capsid proteins enter the nuclei of host epithelial cells and, together with the L2 minor capsid proteins, assemble the replicated viral DNA into virions. We investigated the nuclear import of the L1 major capsid protein of high risk HPV16. When digitonin-permeabilized HeLa cells were incubated with HPV16 L1 capsomeres, the L1 protein was imported into the nucleus in a receptor-mediated manner. HPV16 L1 capsomeres formed complexes with Kap alpha2beta1 heterodimers via interaction with Kap alpha2. Accordingly, nuclear import of HPV16 L1 capsomeres was mediated by Kap alpha2beta1 heterodimers, required RanGDP and free GTP, and was independent of GTP hydrolysis. Remarkably, HPV16 L1 capsomeres also interacted with Kap beta2 and binding of RanGTP to Kap beta2 did not dissociate the HPV16 L1.Kap beta2 complex. Significantly, HPV16 L1 capsomeres inhibited the nuclear import of Kap beta2 and of a Kap beta2-specific M9-containing cargo. These data suggest that, during the productive stage of infection, while the HPV16 L1 major capsid protein enters the nucleus via the Kap alpha2beta1-mediated pathway to assemble the virions, it also inhibits the Kap beta2-mediated nuclear import of host hnRNP A1 protein and, in this way, favors virion formation.
Nelson
Lisa M
LM
Biology Department, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Rose
Robert C
RC
Moroianu
Junona
J
D021581:Active Transport, Cell Nucleus; D036022:Capsid Proteins; D006367:HeLa Cells; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000378:metabolism*; D028961:beta Karyopherins / Q000737:chemistry / Q000502:physiology
D036022:Capsid Proteins; D009856:Oncogene Proteins, Viral; C108121:TNPO1 protein, human; D028961:beta Karyopherins; C063317:L1 protein, Human papillomavirus type 16