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Published on: October 7, 2011
Regulation of host gene expression by J paramyxovirus
Elizabeth R Wrobel1, Jared Jackson1, Mathew Abraham1
1Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
Abstract:
Paramyxoviruses are negative-sense, single-stranded RNA viruses that are associated with numerous diseases in humans and animals. J paramyxovirus (JPV) was first isolated from moribund mice (Mus musculus) with hemorrhagic lung lesions in Australia in 1972. In 2016, JPV was classified into the newly established genus Jeilongvirus. Novel jeilongviruses are being discovered worldwide in wildlife populations. However, the effects of jeilongvirus infection on host gene expression remains uncharacterized. To address this, cellular RNA from JPV-infected mouse fibroblasts was collected at 2, 4, 8, 12, 16, 24, and 48 hours post-infection (hpi) and were sequenced using single-end 75 base pairs (SE75) sequencing chemistry on an Illumina NextSeq platform. Differentially expressed genes (DEGs) between the virus-infected replicates and mock replicates at each timepoint were identified using the Tophat2-Cufflinks-Cuffdiff protocol. At 2 hpi, 11 DEGs were identified in JPV-infected cells, while 1,837 DEGs were detected at 48 hpi. A GO analysis determined that the genes at the earlier timepoints were involved in interferon responses, while there was a shift towards genes that are involved in antigen processing and presentation processes at the later timepoints. At 48 hpi, a KEGG analysis revealed that many of the DEGs detected were involved in pathways that are important for immune responses. qRT-PCR verified that Rtp4, Ifit3, Mx2, and Stat2 were all upregulated during JPV infection, while G0s2 was downregulated. After JPV infection, the expression of inflammatory and antiviral factors in mouse fibroblasts changes significantly. This study provides crucial insight into the different arms of host immunity that mediate Jeilongvirus infection. Understanding the pathogenic mechanisms of Jeilongvirus will lead to better strategies for the prevention and control of potential diseases that may arise from this group of viruses.
Insights
J paramyxovirus (JPV) infection alters host gene expression in mouse fibroblasts, shifting from interferon responses early on to antigen processing later. This reveals key immune pathways involved in Jeilongvirus pathogenesis.
Area of Science:
- Virology
- Immunology
- Genomics
Background:
- Paramyxoviruses cause significant human and animal diseases.
- Jeilongvirus, a genus within Paramyxoviridae, is increasingly found in wildlife.
- The impact of Jeilongvirus on host gene expression is largely unknown.
Purpose of the Study:
- To investigate the host gene expression changes following J paramyxovirus (JPV) infection in mouse fibroblasts.
- To identify specific immune pathways modulated by Jeilongvirus infection.
Main Methods:
- Mouse fibroblasts were infected with JPV and RNA was sequenced at multiple time points (2-48 hours post-infection).
- Differential gene expression analysis was performed using the Tophat2-Cufflinks-Cuffdiff pipeline.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted.
Main Results:
- A significant number of differentially expressed genes (DEGs) were identified, increasing from 11 at 2 hpi to 1,837 at 48 hpi.
- Early JPV infection primarily affected interferon response genes.
- Later stages showed a shift towards genes involved in antigen processing, presentation, and immune response pathways.
- qRT-PCR confirmed upregulation of Rtp4, Ifit3, Mx2, Stat2 and downregulation of G0s2.
Conclusions:
- JPV infection profoundly impacts host gene expression in a time-dependent manner.
- The study elucidates the host immune response mechanisms against Jeilongvirus.
- Findings provide insights for developing strategies against potential jeilongvirus-related diseases.
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