TY  - JOUR
TI  - Vaccinia Virus Infection Requires Maturation of Macropinosomes.
Y1  - 2015/04/14/
AV  - public
VL  - 16
SP  - 814
EP  - 831
IS  - 8
N1  - © 2015 The Authors. Traffic published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
N2  - The prototypic poxvirus, vaccinia virus (VACV), occurs in two infectious forms, mature virions (MVs) and extracellular virions (EVs). Both enter HeLa cells by inducing macropinocytic uptake. Using confocal microscopy, live-cell imaging, targeted RNAi screening, and perturbants of endosome maturation, we analyzed the properties and maturation pathway of the macropinocytic vacuoles containing VACV MVs in HeLa cells. The vacuoles first acquired markers of early endosomes [Rab5, EEA1, and phosphatidylinositol(3)P]. Prior to release of virus cores into the cytoplasm, they contained markers of late endosomes and lysosomes (Rab7a, LAMP1, SNX3). RNAi screening of endocytic cell factors emphasized the importance of late compartments for VACV infection. Follow-up perturbation analysis showed that infection required Rab7a and PIKfyve, confirming that VACV is a late penetrating virus dependent on macropinosome maturation. VACV EV infection was inhibited by depletion of many of the same factors, indicating that both infectious particle forms share the need for late vacuolar conditions for penetration.
ID  - discovery1466174
UR  - http://dx.doi.org/10.1111/tra.12290
JF  - Traffic
A1  - Rizopoulos, Z
A1  - Balistreri, G
A1  - Kilcher, S
A1  - Martin, CK
A1  - Syedbasha, M
A1  - Helenius, A
A1  - Mercer, J
KW  - Endocytosis
KW  -  Macropinocytosis
KW  -  PIKfyve
KW  -  Phosphoinositide exchange
KW  -  Poxvirus
KW  -  Rab conversion
KW  -  Virus entry
ER  -