Actin dynamics regulate multiple endosomal steps during kaposi's sarcoma-associated herpesvirus entry and trafficking in endothelial cells | |
Greene, Whitney1,2; Gao, Shou-Jiang1,2,3,4,5 | |
刊名 | Plos pathogens
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2009-07-01 | |
卷号 | 5期号:7页码:18 |
ISSN号 | 1553-7366 |
DOI | 10.1371/journal.ppat.1000512 |
通讯作者 | Greene, whitney() |
英文摘要 | The role of actin dynamics in clathrin-mediated endocytosis in mammalian cells is unclear. in this study, we define the role of actin cytoskeleton in kaposi's sarcoma-associated herpesvirus (kshv) entry and trafficking in endothelial cells using an immunofluorescence-based assay to visualize viral capsids and the associated cellular components. in contrast to infectivity or reporter assays, this method does not rely on the expression of any viral and reporter genes, but instead directly tracks the accumulation of individual viral particles at the nuclear membrane as an indicator of successful viral entry and trafficking in cells. inhibitors of endosomal acidification reduced both the percentage of nuclei with viral particles and the total number of viral particles docking at the perinuclear region, indicating endocytosis, rather than plasma membrane fusion, as the primary route for kshv entry into endothelial cells. accordingly, a viral envelope protein was only detected on internalized kshv particles at the early but not late stage of infection. inhibitors of clathrin- but not caveolae/lipid raft-mediated endocytosis blocked kshv entry, indicating that clathrin- mediated endocytosis is the major route of kshv entry into endothelial cells. kshv particles were colocalized not only with markers of early and recycling endosomes, and lysosomes, but also with actin filaments at the early time points of infection. consistent with these observations, transferrin, which enters cells by clathrin- mediated endocytosis, was found to be associated with actin filaments together with early and recycling endosomes, and to a lesser degree, with late endosomes and lysosomes. kshv infection induced dynamic actin cytoskeleton rearrangements. disruption of the actin cytoskeleton and inhibition of regulators of actin nucleation such as rho gtpases and arp2/3 complex profoundly blocked kshv entry and trafficking. together, these results indicate an important role for actin dynamics in the internalization and endosomal sorting/trafficking of kshv and clathrin- mediated endocytosis in endothelial cells. |
WOS关键词 | CLATHRIN-MEDIATED ENDOCYTOSIS ; POLARIZED EPITHELIAL-CELLS ; MAMMALIAN-CELLS ; SIMPLEX-VIRUS ; CHOLERA-TOXIN ; N-WASP ; LISTERIA-MONOCYTOGENES ; MICROTUBULE DYNAMICS ; MEMBRANE DYNAMICS ; PRIMARY INFECTION |
WOS研究方向 | Microbiology ; Parasitology ; Virology |
WOS类目 | Microbiology ; Parasitology ; Virology |
语种 | 英语 |
出版者 | PUBLIC LIBRARY SCIENCE |
WOS记录号 | WOS:000269224500028 |
内容类型 | 期刊论文 |
URI标识 | http://www.corc.org.cn/handle/1471x/2375531 |
专题 | 武汉病毒研究所 |
通讯作者 | Greene, Whitney |
作者单位 | 1.Univ Texas Hlth Sci Ctr San Antonio, Tumor Virol Program, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA 2.Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA 3.Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA 4.Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA 5.Chinese Acad Sci, Wuhan Inst Virol, Tumor Virol Grp, Wuhan, Peoples R China |
推荐引用方式 GB/T 7714 | Greene, Whitney,Gao, Shou-Jiang. Actin dynamics regulate multiple endosomal steps during kaposi's sarcoma-associated herpesvirus entry and trafficking in endothelial cells[J]. Plos pathogens,2009,5(7):18. |
APA | Greene, Whitney,&Gao, Shou-Jiang.(2009).Actin dynamics regulate multiple endosomal steps during kaposi's sarcoma-associated herpesvirus entry and trafficking in endothelial cells.Plos pathogens,5(7),18. |
MLA | Greene, Whitney,et al."Actin dynamics regulate multiple endosomal steps during kaposi's sarcoma-associated herpesvirus entry and trafficking in endothelial cells".Plos pathogens 5.7(2009):18. |
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