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Viruses 2017, 9(8), 202; doi:10.3390/v9080202

A Motif in the F Homomorph of Rabbit Haemorrhagic Disease Virus Polymerase Is Important for the Subcellular Localisation of the Protein and Its Ability to Induce Redistribution of Golgi Membranes

1
Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation, Canberra, ACT 2601, Australia
2
Invasive Animals Cooperative Research Centre, University of Canberra, Canberra, ACT 2601, Australia
3
Health Research Institute, University of Canberra, Canberra, ACT 2601, Australia
4
School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, NSW 2052, Australia
5
Institute for Applied Ecology, University of Canberra, Canberra, ACT 2601, Australia
Current address: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
*
Author to whom correspondence should be addressed.
Academic Editor: Andrew Mehle
Received: 22 June 2017 / Revised: 21 July 2017 / Accepted: 21 July 2017 / Published: 1 August 2017
(This article belongs to the Section Animal Viruses)
View Full-Text   |   Download PDF [5710 KB, uploaded 1 August 2017]   |  

Abstract

Rabbit haemorrhagic disease virus (RHDV) is a calicivirus that infects and frequently kills rabbits. Previously, we showed that the RHDV RNA-dependent RNA polymerase (RdRp) is associated with distinct, but yet uncharacterised subcellular structures and is capable of inducing a redistribution of Golgi membranes. In this study, we identified a partially hidden hydrophobic motif that determines the subcellular localisation of recombinant RHDV RdRp in transfected cells. This novel motif, 189LLWGCDVGVAVCAAAVFHNICY210, is located within the F homomorph, between the conserved F3 and A motifs of the core RdRp domain. Amino acid substitutions that decrease the hydrophobicity of this motif reduced the ability of the protein to accumulate in multiple subcellular foci and to induce a rearrangement of the Golgi network. Furthermore, preliminary molecular dynamics simulations suggest that the RHDV RdRp could align with the negatively charged surfaces of biological membranes and undergo a conformational change involving the F homomorph. These changes would expose the newly identified hydrophobic motif so it could immerse itself into the outer leaflet of intracellular membranes. View Full-Text
Keywords: Rabbit haemorrhagic disease virus; RHDV; caliciviruses; RNA-dependent RNA polymerase; Golgi membranes Rabbit haemorrhagic disease virus; RHDV; caliciviruses; RNA-dependent RNA polymerase; Golgi membranes
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MDPI and ACS Style

Urakova, N.; Warden, A.C.; White, P.A.; Strive, T.; Frese, M. A Motif in the F Homomorph of Rabbit Haemorrhagic Disease Virus Polymerase Is Important for the Subcellular Localisation of the Protein and Its Ability to Induce Redistribution of Golgi Membranes. Viruses 2017, 9, 202.

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