DiGiuseppe Stephen, Luszczek Wioleta, Keiffer Timothy R, Bienkowska-Haba Malgorzata, Guion Lucile G M, Sapp Martin J
Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, LSU Health Shreveport, Shreveport, LA 71130.
Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, LSU Health Shreveport, Shreveport, LA 71130
Proc Natl Acad Sci U S A. 2016 May 31;113(22):6289-94. doi: 10.1073/pnas.1600638113. Epub 2016 May 17.
During the entry process, the human papillomavirus (HPV) capsid is trafficked to the trans-Golgi network (TGN), whereupon it enters the nucleus during mitosis. We previously demonstrated that the minor capsid protein L2 assumes a transmembranous conformation in the TGN. Here we provide evidence that the incoming viral genome dissociates from the TGN and associates with microtubules after the onset of mitosis. Deposition onto mitotic chromosomes is L2-mediated. Using differential staining of an incoming viral genome by small molecular dyes in selectively permeabilized cells, nuclease protection, and flotation assays, we found that HPV resides in a membrane-bound vesicle until mitosis is completed and the nuclear envelope has reformed. As a result, expression of the incoming viral genome is delayed. Taken together, these data provide evidence that HPV has evolved a unique strategy for delivering the viral genome to the nucleus of dividing cells. Furthermore, it is unlikely that nuclear vesicles are unique to HPV, and thus we may have uncovered a hitherto unrecognized cellular pathway that may be of interest for future cell biological studies.
在进入过程中，人乳头瘤病毒（HPV）衣壳被转运至反式高尔基体网络（TGN），随后在有丝分裂期间进入细胞核。我们之前证明了次要衣壳蛋白L2在TGN中呈现跨膜构象。在此我们提供证据表明，进入的病毒基因组在有丝分裂开始后从TGN解离并与微管结合。沉积到有丝分裂染色体上是由L2介导的。通过在选择性通透的细胞中用小分子染料对进入的病毒基因组进行差异染色、核酸酶保护和浮选分析，我们发现HPV存在于膜结合囊泡中，直到有丝分裂完成且核膜重新形成。因此，进入的病毒基因组的表达被延迟。综上所述，这些数据提供了证据表明HPV已经进化出一种独特的策略，用于将病毒基因组递送至分裂细胞的细胞核。此外，核囊泡不太可能是HPV特有的，因此我们可能发现了一条迄今未被认识的细胞途径，这可能对未来的细胞生物学研究具有重要意义。
