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Murine norovirus-1 cell entry is mediated through a non-clathrin-, non-caveolae-, dynamin- and cholesterol-dependent pathway

Gerondopoulos, A, Jackson, T, Monaghan, P, Doyle, N and Roberts, LO (2010) Murine norovirus-1 cell entry is mediated through a non-clathrin-, non-caveolae-, dynamin- and cholesterol-dependent pathway Journal of General Virology, 91 (6). 1428 - 1438. ISSN 0022-1317

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Abstract

For many viruses, endocytosis and exposure to the low pH within acidic endosomes is essential for infection. It has previously been reported that FCV uses clathrin-mediated endocytosis for entry into mammalian cells. Here we report that infection of RAW264.7 macrophages, by the closely related murine norovirus-1, does not require the clathrin pathway, as infection was not inhibited by expression of dominant-negative Eps15 or by knock down of the AP-2 complex. Further, infection was not inhibited by reagents that raise endosomal pH. RAW264.7 macrophages were shown not to express caveolin, and flotillin depletion did not inhibit infection, suggesting that caveolae and the flotillin pathway are not required for cell-entry. However, MNV-1 infection was inhibited by methyl--cyclodextrin and the dynamin inhibitor, dynasore. Addition of these drugs to the cells after a period of virus internalisation did not inhibit infection, suggesting the involvement of cholesterol sensitive lipid-rafts and dynamin in the entry mechanism. Macropinocytosis was shown to be active in RAW264.7 macrophages (as indicated by uptake of dextran) and could be blocked by EIPA, which is reported to inhibit this pathway. However, infection was enhanced in the presence of EIPA. Similarly, actin disruption, which also inhibits macropinocytosis, resulted in enhanced infection. These results suggest that macropinocytosis could contribute to virus degradation or that inhibition of macropinocytosis could lead to the up-regulation of other endocytic pathways of virus uptake

Item Type: Article
Uncontrolled Keywords: INDEPENDENT ENDOCYTIC PATHWAY, FELINE-CALICIVIRUS, PLASMA-MEMBRANE, ACTIN POLYMERIZATION, BINDING PROTEIN, VIRUS ENTRY, IN-VIVO, EPS15, MACROPINOCYTOSIS, INTERNALIZATION
Divisions: Faculty of Health and Medical Sciences > Microbial and Cellular Sciences
Depositing User: Symplectic Elements
Date Deposited: 05 Mar 2012 12:48
Last Modified: 23 Sep 2013 19:06
URI: http://epubs.surrey.ac.uk/id/eprint/184880

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