Distinct Cell Transcriptomic Landscapes Upon Henipavirus Infections.

Mingyue Chen,Jie Cui,Lin-Fa Wang,Glenn A Marsh,Mary Tachedjian

doi:10.3389/fmicb.2020.00986

Abstract

Hendra virus (HeV) and Cedar virus (CedV) are henipaviruses, which fall into the Paramyxoviridae family of single-stranded, negative-sense RNA viruses. HeV is classified as a Biosafety Level-4 (BSL-4) agent, as it is highly pathogenic and is often fatal to humans. To date, no HeV prevention or treatment methods for human are available. In contrast, previous experimental infection studies have suggested that CedV is non-pathogenic. Flying foxes (pteropid bats) in Australia are the natural reservoirs of both viruses, but the cellular responses of bats to these viral infections remain unclear. Here, we infected bat and human cells with these viruses. We then examined the total transcriptomic landscapes of the cells at 6 or 24 h post infection. Unexpectedly, despite the close phylogenetic relationship between HeV and CedV, there was a dramatic difference in cellular gene expression patterns in response to the two different infections. It is likely that minor differences in the phosphoprotein (P) gene coding strategy between the two viruses cause the observed incongruence in host transcriptomic divergence and viral lethality. This study greatly expands our understanding of the pathogenic mechanisms of henipaviruses.

Highlights

The fewest differentially expressed genes (DEGs) were identified in Hendra virus (HeV)-infected HeLa cells at 24 hpi (784 genes upregulated and 411 downregulated, as compared to uninfected HeLa cells)
More DEGs were identified in the Cedar virus (CedV)-infected cells than in HeV-infected cells, irrespective of cell type
We examined the expression of IFN-induced protein with the tetratricopeptide repeats (IFIT) during HeV and CedV infection

Summary

INTRODUCTION

Two viruses in the genus Henipavirus (Eaton et al, 2006; Marsh et al, 2012), Hendra (HeV) and Nipah (NiV), are the only known Biosafety Level 4 (BSL-4) pathogens in the family Paramyxoviridae (Marsh et al, 2012). CedV and HeV use different coding strategy of the viral phosphoprotein (P) gene, which play fundamental role in antagonizing the innate immune system of the host (Marsh et al, 2012; Glennon et al, 2015). We used RNA sequencing (RNA-seq) to identify differences in human and bat cell lines after two periods of infection with either HeV or CedV. Both cell lines exhibited a stronger immune response to CedV than to HeV. Our study provides novel insight into the host response to infection with phylogenetically similar, but pathogenically dissimilar viruses

RESULTS

DISCUSSION

MATERIALS AND METHODS