Binding and entry of peste des petits ruminants virus into caprine endometrial epithelial cells profoundly affect early cellular gene expression

Bo Yang,Shuying Chen,Xuefeng Qi,Jingyu Wang,Peilong Jia,Zhijie Chen,Ting Wang,Qinghong Xue

doi:10.1186/s13567-018-0504-3

Abstract

Peste des petits ruminants virus (PPRV), the etiological agent of peste des petits ruminants (PPR), causes an acute or subacute disease in small ruminants. Although abortion is observed in an unusually large proportion of pregnant goats during outbreaks of PPR, the pathogenic mechanism underlying remains unclear. Here, the gene expression profile of caprine endometrial epithelial cells (EECs) infected with PPRV Nigeria 75/1 was determined by DNA microarray to investigate the cellular response immediately after viral entry. The microarray analysis revealed that a total of 146 genes were significantly dysregulated by PPRV internalization within 1 h post-infection (hpi). Of these, 85 genes were upregulated and 61 genes were downregulated. Most of these genes, including NFKB1A, JUNB, and IL1A, have not previously been reported in association with PPRV infection in goats. Following viral replication (24 hpi), the expression of 307 genes were significantly upregulated and that of 261 genes were downregulated. The data for the genes differentially expressed in EECs were subjected to a time sequence profile analysis, gene network analysis and pathway analysis. The gene network analysis showed that 13 genes (EIF2AK3, IL10, TLR4, ZO3, NFKBIB, RAC1, HSP90AA1, SMAD7, ARG2, JUNB, ZFP36, APP, and IL1A) were located in the core of the network. We clearly demonstrate that PPRV infection upregulates the expression of nectin-4 after 1 hpi, which peaked at 24 hpi in EECs. In conclusion, this study demonstrates the early cellular gene expression in the caprine endometrial epithelial cells after the binding and entry of PPRV.

Highlights

Peste des petits ruminants virus (PPRV) is a Morbillivirus of the family Paramyxoviridae, which causes an acute, highly contagious, and fatal disease that primarily affects goats and sheep
The overall changes in the receptor nectin-4 levels expressed in the PPRV-infected cells were consistent with the changes in the PPRV-N expression detected, except that the receptor protein was first detected at 3 hpi and peaked at 24 hpi in the epithelial cells (EECs) (Figures 2B and C)
The present study confirms the same trends in the changes in PPRV-N and nectin-4 expression in PPRV-exposed goat-derived epithelial cells, which implies that PPRV replication has a role in regulating the expression of the receptor nectin-4

Summary

Introduction

Peste des petits ruminants virus (PPRV) is a Morbillivirus of the family Paramyxoviridae, which causes an acute, highly contagious, and fatal disease that primarily affects goats and sheep. PPRV has a well-established lymphatic and epithelial tissue tropism [9, 10]. Similar to Measles virus (MV), PPRV has three cellular receptors: CD46, the protein signaling lymphocyte activation molecule (SLAM or CD150), and the poliovirus receptorlike protein 4 ( known as PVRL4 or nectin-4). Ovine nectin-4 was identified as the epithelial receptor for PPRV. It is predominantly expressed in epithelial tissues and is encoded by multiple haplotypes in sheep breeds around the world [11].

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