Genomic analysis of host – Peste des petits ruminants vaccine viral transcriptome uncovers transcription factors modulating immune regulatory pathways

Abstract

Peste des petits ruminants (PPR), is an acute transboundary viral disease of economic importance, affecting goats and sheep. Mass vaccination programs around the world resulted in the decline of PPR outbreaks. Sungri 96 is a live attenuated vaccine, widely used in Northern India against PPR. This vaccine virus, isolated from goat works efficiently both in sheep and goat. Global gene expression changes under PPR vaccine virus infection are not yet well defined. Therefore, in this study we investigated the host-vaccine virus interactions by infecting the peripheral blood mononuclear cells isolated from goat with PPRV (Sungri 96 vaccine virus), to quantify the global changes in the transcriptomic signature by RNA-sequencing. Viral genome of Sungri 96 vaccine virus was assembled from the PPRV infected transcriptome confirming the infection and demonstrating the feasibility of building a complete non-host genome from the blood transcriptome. Comparison of infected transcriptome with control transcriptome revealed 985 differentially expressed genes. Functional analysis showed enrichment of immune regulatory pathways under PPRV infection. Key genes involved in immune system regulation, spliceosomal and apoptotic pathways were identified to be dysregulated. Network analysis revealed that the protein - protein interaction network among differentially expressed genes is significantly disrupted in infected state. Several genes encoding TFs that govern immune regulatory pathways were identified to co-regulate the differentially expressed genes. These data provide insights into the host - PPRV vaccine virus interactome for the first time. Our findings suggested dysregulation of immune regulatory pathways and genes encoding Transcription Factors (TFs) that govern these pathways in response to viral infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-015-0153-8) contains supplementary material, which is available to authorized users.

Transcriptome analysis reveals common differential and global gene expression profiles in bluetongue virus serotype 16 (BTV-16) infected peripheral blood mononuclear cells (PBMCs) in sheep and goats

“…PBMCs were used in vitro to study the innate immune responses in sheep and goats in response to BTV infection [18]. Recently, global transcriptome analysis was used to understand the molecular events of host virus interactome in PPRV [19], Measles virus [20], [21] and Rinderpest virus [21] infections. However, to the best of our knowledge there are currently no reports on global transcriptome analysis of BTV-host interactome till date.…”

Autophagy enhances the replication of Peste des petits ruminants virus and inhibits caspase-dependent apoptosis in vitro

“…Among the cells subject to PPRV infection, Vero cells are usually used to study PPRV infection in vitro [17,44]. It is well known that PPRV can infect a multitude of host cells, such as sheep kidney epithelial cells [45] (PO cell line) and goat peripheral blood mononuclear cells (PBMCs) [46]. Throughout our study, caprine endometrial epithelial cells were used for the experiments, and we showed that PPRV can successfully replicate in caprine EECs, further confirming the clinical phenomenon of abortions in PPRV-infected goats [3,4]; these data thus provide a theoretical basis for the replication mechanism of PPRV.…”

Systems Perspective of Morbillivirus Replication

“…Pathogenic and nonpathogenic RPV also induce significant differences, with the latter inducing a slightly higher interferon response as well as significant effects on the transcription of genes involved in cell cycle regulation [Nanda et al, 2009]. PPRV infection to PBMCs leads to differential expression of at least 985 genes that are involved in regulating immune regulatory, spliceosomal and apoptotic pathways [Manjunath et al, 2015]. Previously, with a traditional reductionist approach, only handfuls of these genes were known.…”

“…Computational analyses have been used to construct and describe virus-host interactomes [Watanabe and Kawaoka, 2015] which in turn have identified cellular targets for therapeutic intervention [Kumar et al, 2011a]. Such host-virus interactomes have been generated for a wide variety of viruses, including PPRV [Manjunath et al, 2015], and have highlighted the cellular factors that may be important in viral replication, virulence, pathogenesis and immune response [Law et al, 2013]. A metaanalysis of virus-host interactomes identified both common as well as virus-specific host targets, suggesting that a common drug target for multiple viruses can be developed [Watanabe and Kawaoka, 2015].…”

“…Nevertheless, transcriptome analyses of peripheral blood mononuclear cells (PBMCs) following morbillivirus infection [Nanda et al, 2009], including PPRV [Manjunath et al, 2015], have also been analyzed. Transcriptome analyses of bovine dendritic cells following RPV infection (bovine pathogen) and a wild-type MV (human pathogen) suggest that, compared to RPV, MV induces a robust and rapid interferon response.…”