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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019 and caused a global pandemic resulting in millions of deaths and tens of millions of patients positive tests. While studies have shown a D614G mutation in the viral spike protein are more transmissible, the effects of this and other mutations on the host response, especially at the cellular level, are yet to be fully elucidated. In this experiment we infected normal human bronchial epithelial (NHBE) cells with the Washington (D614) strain or the New York (G614) strains of SARS-CoV-2. We generated RNA sequencing data at 6, 12, and 24 hours post-infection (hpi) to improve our understanding of how the intracellular host response differs between infections with these two strains. We analyzed these data with a bioinformatics pipeline that identifies differentially expressed genes (DEGs), enriched Gene Ontology (GO) terms and dysregulated signaling pathways. We detected over 2,000 DEGs, over 600 GO terms, and 29 affected pathways between the two infections. Many of these entities play a role in immune signaling and response. A comparison between strains and time points showed a higher similarity between matched time points than across different time points with the same strain in DEGs and affected pathways, but found more similarity between strains across different time points when looking at GO terms. A comparison of the affected pathways showed that the 24hpi samples of the New York strain were more similar to the 12hpi samples of the Washington strain, with a large number of pathways related to translation being inhibited in both strains. These results suggest that the various mutations contained in the genome of these two viral isolates may cause distinct effects on the host transcriptional response in infected host cells, especially relating to how quickly translation is dysregulated after infection. This comparison of the intracellular host response to infection with these two SARS-CoV-2 isolates suggest that some of the mechanisms associated with more severe disease from these viruses could include virus replication, metal ion usage, host translation shutoff, host transcript stability, and immune inhibition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Scott, Solis-Leal, Lopez, Robison, Berges and Pickett.)

The Coronaviridae is a family of positive-strand RNA viruses that includes SARS-CoV-2, the etiologic agent of the COVID-19 pandemic. Bearing the largest single-stranded RNA genomes in nature, coronaviruses are critically dependent on long-distance RNA-RNA interactions to regulate the viral transcription and replication pathways. Here we experimentally mapped the in vivo RNA-RNA interactome of the full-length SARS-CoV-2 genome and subgenomic mRNAs. We uncovered a network of RNA-RNA interactions spanning tens of thousands of nucleotides. These interactions reveal that the viral genome and subgenomes adopt alternative topologies inside cells and engage in different interactions with host RNAs. Notably, we discovered a long-range RNA-RNA interaction, the FSE-arch, that encircles the programmed ribosomal frameshifting element. The FSE-arch is conserved in the related MERS-CoV and is under purifying selection. Our findings illuminate RNA structure-based mechanisms governing replication, discontinuous transcription, and translation of coronaviruses and will aid future efforts to develop antiviral strategies., Competing Interests: Declaration of Interests The authors declare no competing interests. E.A.M. is a founder and director of STORM Therapeutics. STORM Therapeutics had no role in the design, performance, analysis, interpretation, and writing of the study. O.Z. is a consultant for Evotec Int. Evotec Int. had no role in the design, performance, analysis, interpretation, and writing of the study., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Viruses are the intracellular pathogens that reproduce only in the living cell and manipulate the cellular machinery to produce more viruses. Viral replications can affect cellular genes of the host in multiple cancerous ways. Approximately, 20% of all human oncogenesis is caused by cancer-causing viruses known as oncoviruses. Viral infection causes chronic inflammation leading to cell death, uncontrollable proliferation, and modulated expression of some of the regulatory proteins. Oncogenesis is a multistep phenomenon in which normal host cells are transformed into cancerous cells on the basis of host genetic variability. Oncogenic viruses encode genes that cause viral replication and transformation of the host cells to produce viral proteins and protein complexes. The phenomenon from basic viral infection to tumorigenesis is lengthy due to the involvement of factors like immunity complications, cellular mutations, and exposure to other cancerous agents. The viruses that are involved in human cancer development are Hepatitis B virus (HBV), Hepatitis C virus (HCV), Epstein-Barr virus (EBV), Human papilloma virus (HPV), Kaposi's sarcoma herpes virus (KSHV), and Human T lymphotrophic virus 1 (HTLV-1). This review article summarizes advanced knowledge related to human oncogenic viruses and the molecular mechanisms that lead to tumorigenesis in humans.