Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis.

The novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after emerging in Wuhan, China. Here we analyzed public host and viral RNA sequencing data to better understand how SARS-CoV-2 interacts with human respiratory cells. We identified genes, isoforms and transposable element families that are specifically altered in SARS-CoV-2-infected respiratory cells. Well-known immunoregulatory genes including CSF2, IL32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were upregulated. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and eukaryotic initiation factor 4 (eIF4b). We also identified a viral sequence variant with a statistically significant skew associated with age of infection, that may contribute to intracellular host-pathogen interactions. These findings can help identify host mechanisms that can be targeted by prophylactics and/or therapeutics to reduce the severity of COVID-19.

Oxidative and radiation stress induces transposable element transcription in Drosophila melanogaster.

It has been shown that stressors are capable of activating transposable elements (TEs). Currently, there is a hypothesis that stress activation of TEs may be involved in adaptive evolution, favouring the increase in genetic variability when the population is under adverse conditions. However, TE activation under stress is still poorly understood. In the present study, we estimated the fraction of differentially expressed TEs (DETEs) under ionizing radiation (144, 360 and 864 Gy) and oxidative stress (dioxin, formaldehyde and toluene) treatments. The stress intensity of each treatment was estimated by measuring the number of differentially expressed genes, and we show that several TEs families are activated by stress whereas others are repressed. The proportion of DETEs was positively related to stress intensity. However, even under the strongest stress, only a small fraction of TE families were activated (9.28%) and 17.72% were repressed. Considering all treatments together, the activated proportion was 19.83%. Nevertheless, as several TEs are incomplete or degenerated, only 10.55% of D. melanogaster mobilome is, at same time, activated by the stressors and able to transpose or at least code a protein. Thus, our study points out that although stress activates TEs, it is not a generalized activation process, and for some families, the stress induces repression.