Vaccinia virus dissemination requires p21-activated kinase 1

Luciana G. Andrade, Jonas D. Albarnaz, Fernanda L.B. Mügge, Bruna A. David, Jônatas S. Abrahão, Flávio G. da Fonseca, Erna G. Kroon, Gustavo B. Menezes, Douglas McFadden, Cláudio A. Bonjardim

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2991-3002
Number of pages12
JournalArchives of Virology
Volume161
Issue number11
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

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p21-Activated Kinases
Vaccinia virus
Virion
Virus Internalization
Actins
Orthopoxvirus
Actin Cytoskeleton
Microtubules
Electron Scanning Microscopy
Viruses

ASJC Scopus subject areas

  • Virology

Cite this

Andrade, L. G., Albarnaz, J. D., Mügge, F. L. B., David, B. A., Abrahão, J. S., da Fonseca, F. G., ... Bonjardim, C. A. (2016). Vaccinia virus dissemination requires p21-activated kinase 1. Archives of Virology, 161(11), 2991-3002. https://doi.org/10.1007/s00705-016-2996-3

Vaccinia virus dissemination requires p21-activated kinase 1. / 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, Douglas; Bonjardim, Cláudio A.

In: Archives of Virology, Vol. 161, No. 11, 01.11.2016, p. 2991-3002.

Research output: Contribution to journalArticle

Andrade, LG, Albarnaz, JD, Mügge, FLB, David, BA, Abrahão, JS, da Fonseca, FG, Kroon, EG, Menezes, GB, McFadden, D & Bonjardim, CA 2016, 'Vaccinia virus dissemination requires p21-activated kinase 1', Archives of Virology, vol. 161, no. 11, pp. 2991-3002. https://doi.org/10.1007/s00705-016-2996-3
Andrade LG, Albarnaz JD, Mügge FLB, David BA, Abrahão JS, da Fonseca FG et al. Vaccinia virus dissemination requires p21-activated kinase 1. Archives of Virology. 2016 Nov 1;161(11):2991-3002. https://doi.org/10.1007/s00705-016-2996-3
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, Douglas ; Bonjardim, Cláudio A. / Vaccinia virus dissemination requires p21-activated kinase 1. In: Archives of Virology. 2016 ; Vol. 161, No. 11. pp. 2991-3002.
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