title: Comparative and temporal transcriptome analysis of peste des petits ruminants virus infected goat peripheral blood mononuclear cells.
abstract: Peste des petits ruminanats virus (PPRV), a morbillivirus causes an acute, highly contagious disease - peste des petits ruminants (PPR), affecting goats and sheep. Sungri/96 vaccine strain is widely used for mass vaccination programs in India against PPR and is considered the most potent vaccine providing long-term immunity. However, occurrence of outbreaks due to emerging PPR viruses may be a challenge. In this study, the temporal dynamics of immune response in goat peripheral blood mononuclear cells (PBMCs) infected with Sungri/96 vaccine virus was investigated by transcriptome analysis. Infected goat PBMCs at 48h and 120h post infection revealed 2540 and 2000 differentially expressed genes (DEGs), respectively, on comparison with respective controls. Comparison of the infected samples revealed 1416 DEGs to be altered across time points. Functional analysis of DEGs reflected enrichment of TLR signaling pathways, innate immune response, inflammatory response, positive regulation of signal transduction and cytokine production. The upregulation of innate immune genes during early phase (between 2-5 days) viz. interferon regulatory factors (IRFs), tripartite motifs (TRIM) and several interferon stimulated genes (ISGs) in infected PBMCs and interactome analysis indicated induction of broad-spectrum anti-viral state. Several Transcription factors - IRF3, FOXO3 and SP1 that govern immune regulatory pathways were identified to co-regulate the DEGs. The results from this study, highlighted the involvement of both innate and adaptive immune systems with the enrichment of complement cascade observed at 120h p.i., suggestive of a link between innate and adaptive immune response. Based on the transcriptome analysis and qRT-PCR validation, an in vitro mechanism for the induction of ISGs by IRFs in an interferon independent manner to trigger a robust immune response was predicted in PPRV infection.
authors.affiliation: Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India; School of Informatics and Computing, Indiana University Purdue University, 719 Indiana Ave Ste 319, Walker Plaza Building, Indianapolis, IN 46202, United States. Electronic address: smanju712@gmail.com.
authors.forename: Siddappa
authors.initials: S
authors.lastname: Manjunath
authors.affiliation: Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India. Electronic address: bpmishra_1@hotmail.com.
authors.forename: Bishnu Prasad
authors.initials: BP
authors.lastname: Mishra
authors.affiliation: Division of Biological Products, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India. Electronic address: binachauhanmishra@hotmail.com.
authors.forename: Bina
authors.initials: B
authors.lastname: Mishra
authors.affiliation: Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India. Electronic address: rush2aditya@gmail.com.
authors.forename: Aditya Prasad
authors.initials: AP
authors.lastname: Sahoo
authors.affiliation: Division of Biological Standardization, ICAR-Indian Veterinary Research Institute, Izatnagar, 243122, India. Electronic address: aktiwari63@yahoo.com.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Tiwari
authors.affiliation: Division of Virology, ICAR-Indian Veterinary Research Institute (IVRI), Mukteswar Campus, Nainital, Uttaranchal, 263138, India. Electronic address: kaushalvirol@gmail.com.
authors.forename: Kaushal Kishore
authors.initials: KK
authors.lastname: Rajak
authors.affiliation: Division of Virology, ICAR-Indian Veterinary Research Institute (IVRI), Mukteswar Campus, Nainital, Uttaranchal, 263138, India. Electronic address: drchelva@gmail.com.
authors.forename: D
authors.initials: D
authors.lastname: Muthuchelvan
authors.affiliation: Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India. Electronic address: shikhasaxenaivri@gmail.com.
authors.forename: Shikha
authors.initials: S
authors.lastname: Saxena
authors.affiliation: Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India. Electronic address: lakshman.ivri@gmail.com.
authors.forename: Lakshman
authors.initials: L
authors.lastname: Santra
authors.affiliation: Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India. Electronic address: dramitr.sahu@gmail.com.
authors.forename: Amit Ranjan
authors.initials: AR
authors.lastname: Sahu
authors.affiliation: Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India. Electronic address: wanisajad759@gmail.com.
authors.forename: Sajad Ahmad
authors.initials: SA
authors.lastname: Wani
authors.affiliation: Division of Biological Products, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India. Electronic address: rpsingh@dr.com.
authors.forename: R P
authors.initials: RP
authors.lastname: Singh
authors.affiliation: ARIS Cell, ICAR-Indian Veterinary Research Institute (IVRI), Mukteswar Campus, Nainital, Uttaranchal, 263138, India. Electronic address: ypivri@gmail.com.
authors.forename: Y P
authors.initials: YP
authors.lastname: Singh
authors.affiliation: Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India. Electronic address: arunabioinfo@gmail.com.
authors.forename: Aruna
authors.initials: A
authors.lastname: Pandey
authors.affiliation: Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India. Electronic address: kanchansonam@gmail.com.
authors.forename: Sonam
authors.initials: S
authors.lastname: Kanchan
authors.affiliation: Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India. Electronic address: rks_virology@gmail.com.
authors.forename: R K
authors.initials: RK
authors.lastname: Singh
authors.affiliation: Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India. Electronic address: gandham71@gmail.com.
authors.forename: Gandham Ravi
authors.initials: GR
authors.lastname: Kumar
authors.affiliation: School of Informatics and Computing, Indiana University Purdue University, 719 Indiana Ave Ste 319, Walker Plaza Building, Indianapolis, IN 46202, United States; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, 5021 Health Information and Translational Sciences (HITS), 410 West 10th Street, Indianapolis, IN, 46202, United States; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Medical Research and Library Building, 975 West Walnut Street, Indianapolis, IN, 46202, United States. Electronic address: scjanga@iupui.edu.
authors.forename: Sarath Chandra
authors.initials: SC
authors.lastname: Janga
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D000071316:Forkhead Box Protein O3 / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015511:Goat Diseases / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D006041:Goats; D007113:Immunity, Innate / Q000187:drug effects; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D029021:Peste-des-Petits-Ruminants / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D018107:Peste-des-petits-ruminants virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D059467:Transcriptome / Q000276:immunology*; D014611:Vaccination / Q000662:veterinary*; D014709:Vero Cells; D014765:Viral Vaccines / Q000008:administration & dosage
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D000071316:Forkhead Box Protein O3; D007136:Immunoglobulins; D050835:Interferon Regulatory Factors; C090698:SP1 antigen; D014765:Viral Vaccines
keywords: PBMCs; PPRV; Protein-protein interaction networks; RNA-sequencing; Transcription factors; Transcriptome