Alterations in the host transcriptome in vitro following Rift Valley fever virus infection

Abstract

Rift Valley fever virus (RVFV) causes major outbreaks among livestock, characterized by “abortion storms” in which spontaneous abortion occurs in almost 100% of pregnant ruminants. Humans can also become infected with mild symptoms that can progress to more severe symptoms, such as hepatitis, encephalitis, and hemorrhagic fever. The goal of this study was to use RNA-sequencing (RNA-seq) to analyze the host transcriptome in response to RVFV infection. G2/M DNA damage checkpoint, ATM signaling, mitochondrial dysfunction, regulation of the antiviral response, and integrin-linked kinase (ILK) signaling were among the top altered canonical pathways with both the attenuated MP12 strain and the fully virulent ZH548 strain. Although several mRNA transcripts were highly upregulated, an increase at the protein level was not observed for the selected genes, which was at least partially due to the NSs dependent block in mRNA export. Inhibition of ILK signaling, which is involved in cell motility and cytoskeletal reorganization, resulted in reduced RVFV replication, indicating that this pathway is important for viral replication. Overall, this is the first global transcriptomic analysis of the human host response following RVFV infection, which could give insight into novel host responses that have not yet been explored.

In vitro shared transcriptomic responses of Aedes aegypti to arboviral infections: example of dengue and Rift Valley fever viruses

“…The cells were grown at 28 °C in Schneider's Drosophila medium (Gibco Life Technologies) supplemented with 10% FBS (Gibco Life Technologies), 1% L-glutamine 1mM, 1% penicillin-streptomycin (Gibco Life Technologies). Aag2 cells (2 × 10 6 cells/well in a 24-well format plate) were infected either at a multiplicity of infection (MOI) of 0.1 for RVFV or at a MOI of 1 for DENV based on the literature [29,30]. Viruses were allowed to propagate for 24 h and 6 days to assess early and late genes expression.…”

Global Transcriptional Response to CRISPR/Cas9-AAV6-Based Genome Editing in CD34+ Hematopoietic Stem and Progenitor Cells

“…Such global transcriptional and translational repression has been reported as a result of the type I interferon response. 34,35 Our genome-editing protocol used Cas9 to successfully initiate DSB breaks, as indicated by significant indel formation ( Figure 1A). As a consequence, it is not surprising that we observed a DNA damage response (DDR) signature that was most apparent in Cas9 RNP samples.…”

Transcriptome profiling in Rift Valley fever virus infected cells reveals modified transcriptional and alternative splicing programs

“…However, relatively few mRNA-seq studies to date have characterized the host response to viral infection. The studies that have risen to this challenge have revealed novel insights into host-pathogen dynamics [14–18]. A deeper understanding of the host response to viral infection will contribute to the development of effective treatment options and targeted therapies.…”