Ebola Virus Enters Host Cells by Macropinocytosis and Clathrin-Mediated Endocytosis

被引：187

作者：

Aleksandrowicz, Paulina ^{[1
,2
,3
]}

Marzi, Andrea ^{[4
]}

Biedenkopf, Nadine ^{[5
]}

Beimforde, Nadine ^{[1
]}

Becker, Stephan ^{[5
]}

Hoenen, Thomas ^{[5
]}

Feldmann, Heinz ^{[4
,6
]}

Schnittler, Hans-Joachim ^{[1
]}

机构：

[1] Univ Munster, Inst Anat & Vaskulaere Biol, D-48149 Munster, Germany

[2] Tech Univ Dresden, Inst Physiol, Dresden, Germany

[3] Tech Univ Dresden, MTZ Imaging Facil, Dresden, Germany

[4] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA

[5] Univ Marburg, Inst Virol, D-35032 Marburg, Germany

[6] Publ Hlth Agcy Canada, Special Pathogens Program, Natl Microbiol Lab, Winnipeg, MB, Canada

来源：

JOURNAL OF INFECTIOUS DISEASES | 2011年 / 204卷

基金：

美国国家卫生研究院;

关键词：

BARRIER FUNCTION; CELLULAR ENTRY; GLYCOPROTEINS; PARTICLES; INFECTION; MARBURG; DYNAMIN; MACROPHAGES; ACTIVATION; INHIBITORS;

D O I：

10.1093/infdis/jir326

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Virus entry into host cells is the first step of infection and a crucial determinant of pathogenicity. Here we show that Ebola virus-like particles (EBOV-VLPs) composed of the glycoprotein GP(1,2) and the matrix protein VP40 use macropinocytosis and clathrin-mediated endocytosis to enter cells. EBOV-VLPs applied to host cells induced actin-driven ruffling and enhanced FITC-dextran uptake, which indicated macropinocytosis as the main entry mechanism. This was further supported by inhibition of entry through inhibitors of actin polymerization (latrunculin A), Na(+)/H(+)-exchanger (EIPA), and PI3-kinase (wortmannin). A fraction of EBOV-VLPs, however, colocalized with clathrin heavy chain (CHC), and VLP uptake was reduced by CHC small interfering RNA transfection and expression of the dominant negative dynamin II-K44A mutant. In contrast, we found no evidence that EBOV-VLPs enter cells via caveolae. This work identifies macropinocytosis as the major, and clathrin-dependent endocytosis as an alternative, entry route for EBOV particles. Therefore, EBOV seems to utilize different entry pathways depending on both cell type and virus particle size.

引用

页码：S957 / S967

页数：11