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Viruses 2019, 11(2), 128; https://doi.org/10.3390/v11020128

Angiomotin-Like 1 Links Paramyxovirus M Proteins to NEDD4 Family Ubiquitin Ligases

1
Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA
2
Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA 16802, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 14 January 2019 / Revised: 28 January 2019 / Accepted: 30 January 2019 / Published: 31 January 2019
(This article belongs to the Section Animal Viruses)
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Abstract

To define the links between paramyxovirus budding and cellular ESCRT machinery, we previously identified angiomotin-like 1 (AMOTL1) in a screen for host factors that bind to the matrix (M) protein of parainfluenza virus 5 (PIV5). This protein harbors three L/PPXY sequences, allowing it to interact with WW domain containing proteins including NEDD4 family members. We hypothesize that paramyxoviruses use AMOTL1 as a linker to indirectly recruit the same NEDD4 ubiquitin ligases for budding that other enveloped viruses recruit directly through their PPXY late domains. In support of this hypothesis, we found that AMOTL1 could link together M proteins and NEDD4 family proteins in three-way co-IP experiments. Both PIV5 and mumps virus M proteins could be linked to the NEDD4 family proteins NEDD4-1, NEDD4L, and NEDL1, provided that AMOTL1 was co-expressed as a bridging protein. AMOT and AMOTL2 could not substitute for AMOTL1, as they lacked the ability to bind with paramyxovirus M proteins. Attachment of a PPXY late domain sequence to PIV5 M protein obviated the need for AMOTL1 as a linker between M and NEDD4 proteins. Together, these results suggest a novel host factor recruitment strategy for paramyxoviruses to achieve particle release. View Full-Text
Keywords: paramyxovirus; assembly; budding; late domain; PPXY; angiomotin; AMOTL1; NEDD4 paramyxovirus; assembly; budding; late domain; PPXY; angiomotin; AMOTL1; NEDD4
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Ray, G.; Schmitt, P.T.; Schmitt, A.P. Angiomotin-Like 1 Links Paramyxovirus M Proteins to NEDD4 Family Ubiquitin Ligases. Viruses 2019, 11, 128.

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