Measles Virus Matrix Protein Inhibits Host Cell Transcription.

Xuelian Yu,Shadi Shahriari,Reena Ghildyal,Hong-Mei Li,Alexander F Palazzo

doi:10.1371/journal.pone.0161360

Xuelian Yu, Shadi Shahriari + Show 3 more

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https://doi.org/10.1371/journal.pone.0161360

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Abstract

Measles virus (MeV) is a highly contagious virus that still causes annual epidemics in developing countries despite the availability of a safe and effective vaccine. Additionally, importation from endemic countries causes frequent outbreaks in countries where it has been eliminated. The M protein of MeV plays a key role in virus assembly and cytopathogenesis; interestingly, M is localised in nucleus, cytoplasm and membranes of infected cells. We have used transient expression of M in transfected cells and in-cell transcription assays to show that only some MeV M localizes to the nucleus, in addition to cell membranes and the cytoplasm as previously described, and can inhibit cellular transcription via binding to nuclear factors. Additionally, MeV M was able to inhibit in vitro transcription in a dose-dependent manner. Importantly, a proportion of M is also localized to nucleus of MeV infected cells at early times in infection, correlating with inhibition of cellular transcription. Our data show, for the first time, that MeV M may play a role early in infection by inhibiting host cell transcription.

Highlights

Measles virus (MeV) is a negative sense RNA virus belonging to the morbillivirus genus of Paramyxoviridae family and is the causative agent of measles
A proportion of MeVM is localised to the nucleus through binding to chromatin When expressed in COS-7 cells, GFP-MeVM localized predominantly to the plasma membrane and diffused throughout the cytoplasm, as expected [17]
To determine if the nuclear localization of GFP-MeVM was indicative of the subcellular localization of M in infected cells, we probed the localization of M in MeV infected cells at various times post infection up to 18 h p.i. followed by Confocal laser scanning microscopy (CLSM) (Fig 1C)

Summary

Introduction

Measles virus (MeV) is a negative sense RNA virus belonging to the morbillivirus genus of Paramyxoviridae family and is the causative agent of measles. The non-segmented negative-sense RNA genome of MeV contains six genes encoding structural proteins, the nucleocapsid (N), phospho- (P), matrix (M), fusion (F), hemagglutinin (H), and large (L) proteins [4]. H and F proteins are surface glycoproteins responsible for virus attachment to and entry into target cells. The genome is encapsidated by the N protein into a nucleocapsid; L and P proteins constitute the viral RNA-dependent RNA polymerase which associates with the nucleocapsid and thereby forms the ribonucleoprotein (RNP) complex [4]. M protein is located in the inner layer of the viral envelope and plays a key role in virus

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