Vaccinia virus dissemination requires p21-activated kinase 1

The orthopoxvirus vaccinia virus (VACV) interacts with both actin and microtubule cytoskeletons in order to generate and spread progeny virions. Here, we present evidence demonstrating the involvement of PAK1 (p21-activated kinase 1) in the dissemination of VACV. Although PAK1 activation has previou...

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Bibliographic Details
Published in:Archives of virology 2016-11, Vol.161 (11), p.2991-3002
Main Authors: Andrade, Luciana G., Albarnaz, Jonas D., Mügge, Fernanda L. B., David, Bruna A., Abrahão, Jônatas S., da Fonseca, Flávio G., Kroon, Erna G., Menezes, Gustavo B., McFadden, Grant, Bonjardim, Cláudio A.
Format: Article
Language:English
Subjects:
Actin
Animals
Biological Transport
Biomedical and Life Sciences
Biomedicine
Cells, Cultured
Endocytosis
Host-Pathogen Interactions
Infectious Diseases
Medical Microbiology
Mice
Mice, Knockout
Microscopy, Confocal
Microscopy, Electron, Scanning
Original Article
p21-activated kinase
p21-activated kinase 1
p21-Activated Kinases - genetics
p21-Activated Kinases - metabolism
Poxviridae
Scanning electron microscopy
Vaccinia virus
Vaccinia virus - physiology
Virions
Virology
Virus Internalization
Viruses
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Summary:The orthopoxvirus vaccinia virus (VACV) interacts with both actin and microtubule cytoskeletons in order to generate and spread progeny virions. Here, we present evidence demonstrating the involvement of PAK1 (p21-activated kinase 1) in the dissemination of VACV. Although PAK1 activation has previously been associated with optimal VACV entry via macropinocytosis, its absence does not affect the production of intracellular mature virions (IMVs) and extracellular enveloped virions (EEVs). Our data demonstrate that low-multiplicity infection of PAK1 -/- MEFs leads to a reduction in plaque size followed by decreased production of both IMVs and EEVs, strongly suggesting that virus spread was impaired in the absence of PAK1. Confocal and scanning electron microscopy showed a substantial reduction in the amount of VACV-induced actin tails in PAK1 -/- MEFs, but no significant alteration in the total amount of cell-associated enveloped virions (CEVs). Furthermore, the decreased VACV dissemination in PAK1 -/- cells was correlated with the absence of phosphorylated ARPC1 (Thr21), a downstream target of PAK1 and a key regulatory subunit of the ARP2/3 complex, which is necessary for the formation of actin tails and viral spread. We conclude that PAK1, besides its role in virus entry, also plays a relevant role in VACV dissemination.
ISSN:0304-8608
1432-8798
DOI:10.1007/s00705-016-2996-3