Eisa, Mohamed; Loucif, Hamza; van Grevenynghe, Julien 
ORCID: https://orcid.org/0000-0002-2952-4081 et Pearson, Angela ORCID: https://orcid.org/0000-0002-5997-2846
(2021).
Entry of the varicellovirus Canid herpesvirus 1 into Madin-Darby canine kidney epithelial cells is pH-independent and occurs via a macropinocytosis-like mechanism but without increase in fluid uptake
Cellular Microbiology
, vol. 23
, nº 12e13398.
pp. 1-11.
DOI: 10.1111/cmi.13398.
Résumé
Canid herpesvirus 1 (CHV-1) is a Varicellovirus that causes self-limiting infections in adult dogs but morbidity and mortality in puppies. Using a multipronged approach, we discovered the CHV-1 entry pathway into Madin-Darby canine kidney (MDCK) epithelial cells. We found that CHV-1 triggered extensive host cell membrane lamellipodial ruffling and rapid internalization of virions in large, uncoated vacuoles, suggestive of macropinocytosis. Treatment with inhibitors targeting key macropinocytosis factors, including inhibitors of Na(+) /H(+) exchangers, F-actin, myosin light-chain kinase, protein kinase C, p21-activated kinase, phosphatidylinositol-3-kinase, and focal adhesion kinase, significantly reduced viral replication. Moreover, the effect was restricted to exposure to the inhibitors early in infection, confirming a role for the macropinocytic machinery during entry. The profile of inhibitors also suggested a role for signaling via integrins and receptor tyrosine kinases in viral entry. In contrast, inhibitors of clathrin, caveolin, microtubules, and endosomal acidification did not affect CHV-1 entry into MDCK cells. We found that the virus colocalized with the fluid phase uptake marker dextran; however, surprisingly, CHV-1 infection did not enhance the uptake of dextran. Thus, our results indicate that CHV-1 uses a macropinocytosis-like, pH-independent entry pathway into MDCK cells, which nevertheless is not based on stimulation of fluid uptake. This article is protected by copyright. All rights reserved.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 23 juin 2022 02:25 |
| Dernière modification: | 23 juin 2022 02:25 |
| URI: | https://espace.inrs.ca/id/eprint/12331 |
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