Host-Driven Phosphorylation Appears to Regulate the Budding Activity of the Lassa Virus Matrix Protein

Pathogens

MarionE. Weir¹  BryanA. Ballif¹  EmilyA. Bruce²  Philip Eisenhauer²  ChristopherM. Ziegler²  Inessa Manuelyan²  Jason Botten² 

[1] Department of Biology, University of Vermont, Burlington, VT 05405, USA;Department of Medicine, Division of Immunobiology, University of Vermont, Burlington, VT 05405, USA;

关键词: Lassa virus;    Z protein;    late domain;    PPXY;    budding;    release;    matrix protein;    phosphorylation;    arenavirus;    mass spectrometry;   

DOI  :  10.3390/pathogens7040097

来源: DOAJ

【 摘 要 】

Lassa mammarenavirus (LASV) is an enveloped RNA virus that can cause Lassa fever, an acute hemorrhagic fever syndrome associated with significant morbidity and high rates of fatality in endemic regions of western Africa. The arenavirus matrix protein Z has several functions during the virus life cycle, including coordinating viral assembly, driving the release of new virus particles, regulating viral polymerase activity, and antagonizing the host antiviral response. There is limited knowledge regarding how the various functions of Z are regulated. To investigate possible means of regulation, mass spectrometry was used to identify potential sites of phosphorylation in the LASV Z protein. This analysis revealed that two serines (S18, S98) and one tyrosine (Y97) are phosphorylated in the flexible N- and C-terminal regions of the protein. Notably, two of these sites, Y97 and S98, are located in (Y97) or directly adjacent to (S98) the PPXY late domain, an important motif for virus release. Studies with non-phosphorylatable and phosphomimetic Z proteins revealed that these sites are important regulators of the release of LASV particles and that host-driven, reversible phosphorylation may play an important role in the regulation of LASV Z protein function.

【 授权许可】

Unknown