Loss of actin-based motility impairs ectromelia virus release in vitro but is not critical to spread in vivo

Melanie Laura Duncan; Jacquelyn Horsington; Preethi Eldi; Zahrah Al Rumaih; Gunasegaran Karupiah; Timothy P. Newsome

doi:10.3390/v10030111

Loss of actin-based motility impairs ectromelia virus release in vitro but is not critical to spread in vivo

Melanie Laura Duncan, Jacquelyn Horsington, Preethi Eldi, Zahrah Al Rumaih, Gunasegaran Karupiah, Timothy P. Newsome^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

Ectromelia virus (ECTV) is an orthopoxvirus and the causative agent of mousepox. Like other poxviruses such as variola virus (agent of smallpox), monkeypox virus and vaccinia virus (the live vaccine for smallpox), ECTV promotes actin-nucleation at the surface of infected cells during virus release. Homologs of the viral protein A36 mediate this function through phosphorylation of one or two tyrosine residues that ultimately recruit the cellular Arp2/3 actin-nucleating complex. A36 also functions in the intracellular trafficking of virus mediated by kinesin-1. Here, we describe the generation of a recombinant ECTV that is specifically disrupted in actin-based motility allowing us to examine the role of this transport step in vivo for the first time. We show that actin-based motility has a critical role in promoting the release of virus from infected cells in vitro but plays a minor role in virus spread in vivo. It is likely that loss of microtubule-dependent transport is a major factor for the attenuation observed when A36R is deleted.

Original language	English
Article number	111
Journal	Viruses
Volume	10
Issue number	3
DOIs	https://doi.org/10.3390/v10030111
Publication status	Published - 5 Mar 2018

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@article{4f16f6f84fe44f288a6d20d63bbcd527,

title = "Loss of actin-based motility impairs ectromelia virus release in vitro but is not critical to spread in vivo",

abstract = "Ectromelia virus (ECTV) is an orthopoxvirus and the causative agent of mousepox. Like other poxviruses such as variola virus (agent of smallpox), monkeypox virus and vaccinia virus (the live vaccine for smallpox), ECTV promotes actin-nucleation at the surface of infected cells during virus release. Homologs of the viral protein A36 mediate this function through phosphorylation of one or two tyrosine residues that ultimately recruit the cellular Arp2/3 actin-nucleating complex. A36 also functions in the intracellular trafficking of virus mediated by kinesin-1. Here, we describe the generation of a recombinant ECTV that is specifically disrupted in actin-based motility allowing us to examine the role of this transport step in vivo for the first time. We show that actin-based motility has a critical role in promoting the release of virus from infected cells in vitro but plays a minor role in virus spread in vivo. It is likely that loss of microtubule-dependent transport is a major factor for the attenuation observed when A36R is deleted.",

keywords = "A36, Actin-based motility, Arp2/3 complex, Viral release, Virus transport",

author = "Duncan, {Melanie Laura} and Jacquelyn Horsington and Preethi Eldi and {Al Rumaih}, Zahrah and Gunasegaran Karupiah and Newsome, {Timothy P.}",

note = "Publisher Copyright: {\textcopyright} 2018 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2018",

month = mar,

day = "5",

doi = "10.3390/v10030111",

language = "English",

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AU - Duncan, Melanie Laura

AU - Horsington, Jacquelyn

AU - Eldi, Preethi

AU - Al Rumaih, Zahrah

AU - Karupiah, Gunasegaran

AU - Newsome, Timothy P.

PY - 2018/3/5

Y1 - 2018/3/5

N2 - Ectromelia virus (ECTV) is an orthopoxvirus and the causative agent of mousepox. Like other poxviruses such as variola virus (agent of smallpox), monkeypox virus and vaccinia virus (the live vaccine for smallpox), ECTV promotes actin-nucleation at the surface of infected cells during virus release. Homologs of the viral protein A36 mediate this function through phosphorylation of one or two tyrosine residues that ultimately recruit the cellular Arp2/3 actin-nucleating complex. A36 also functions in the intracellular trafficking of virus mediated by kinesin-1. Here, we describe the generation of a recombinant ECTV that is specifically disrupted in actin-based motility allowing us to examine the role of this transport step in vivo for the first time. We show that actin-based motility has a critical role in promoting the release of virus from infected cells in vitro but plays a minor role in virus spread in vivo. It is likely that loss of microtubule-dependent transport is a major factor for the attenuation observed when A36R is deleted.

AB - Ectromelia virus (ECTV) is an orthopoxvirus and the causative agent of mousepox. Like other poxviruses such as variola virus (agent of smallpox), monkeypox virus and vaccinia virus (the live vaccine for smallpox), ECTV promotes actin-nucleation at the surface of infected cells during virus release. Homologs of the viral protein A36 mediate this function through phosphorylation of one or two tyrosine residues that ultimately recruit the cellular Arp2/3 actin-nucleating complex. A36 also functions in the intracellular trafficking of virus mediated by kinesin-1. Here, we describe the generation of a recombinant ECTV that is specifically disrupted in actin-based motility allowing us to examine the role of this transport step in vivo for the first time. We show that actin-based motility has a critical role in promoting the release of virus from infected cells in vitro but plays a minor role in virus spread in vivo. It is likely that loss of microtubule-dependent transport is a major factor for the attenuation observed when A36R is deleted.

KW - A36

KW - Actin-based motility

KW - Arp2/3 complex

KW - Viral release

KW - Virus transport

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U2 - 10.3390/v10030111

DO - 10.3390/v10030111

M3 - Article

SN - 1999-4915

VL - 10

JO - Viruses

JF - Viruses

IS - 3

M1 - 111

ER -

Loss of actin-based motility impairs ectromelia virus release in vitro but is not critical to spread in vivo

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