Time-course of transcriptome response to respiratory syncytial virus infection in lung epithelium cells

Abstract

Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory tract infection in infants. Winter outbreaks in Chile result in 5% of infected children hospitalized, with 0.01% mortality. Increased evidence indicates that viral and host factors modulate the severity of infection. Using DNA microarrays, we characterized the genome-wide transcriptional response of lung mucoepidermoid cells (NCI-H292) at 0, 24, 48, 72 and 96 hours post-infection (hpi) with a single dose of RSV/A. During the whole studied period, a bi-phasic gene expression profile was observed by a total of 330 differentially expressed genes. About 60% of them were up-regulated between 24-72 hpi and then turned-off at 96 hpi. This transient, early gene expression pattern was significantly enriched in biological processes like interferon signaling, antigen processing and presentation, double-stranded RNA binding and chemokine activity. We detected 27 common genes up-regulated between 24-72 hpi, from which IFIT1, IFI44, MX1, CXCL11 and OAS1 had the highest expression. The second pattern comprised over 120 genes, which remained silenced until 72 hpi, but were steeply up-regulated by 96 hpi. Biological processes of this late-response profile included cell cycle division and microtubule cytoskeleton organization. Conversely, the genes belonging to virus response pathway showed a decreased expression at 96 hpi. We conclude that RSV induces an early innate immune activation profile response until 72 hpi. Thereafter, the viral response is inhibited, leading to host cell recovery. The presented cellular model allows to study the specific pathways involved in elimination of infection at prolonged time intervals and their subsequent analysis in severe RSV disease of infants and/or older adults.

Microbiome-Transcriptome Interactions Related to Severity of Respiratory Syncytial Virus Infection

“…This included IFITM1 and IFITM2, which are known to inhibit the infection and replication of respiratory syncytial virus 27,28 , IFI27, a known biomarker for RSV 29 , and IRF7, a gene associated with suppression of innate immunity response 30 . Other genes with known associations to RSV and higher expression in the acute visit included SOCS3 31 , MX1 32 , and the ISGylation pathway genes USP18 and ISG15 33 . Our analysis also identified several genes with higher expression in the follow-up visit, including MS4A1, which encodes the CD20 protein, and MCOLN1.…”

Mutation of Respiratory Syncytial Virus G Protein’s CX3C Motif Attenuates Infection in Cotton Rats and Primary Human Airway Epithelial Cells

“…The RSV/A2- compared to r19F-infected animals also had significantly lower levels of these lung mRNAs at day five post primary infection. The MX1 expression is controlled by Type I and III interferons, and it is known to inhibit negative-strand RNA viruses [39] It has been shown to increase in RSV infection of a human immortalized lung cell line, certain of its alleles associated with severity of RSV disease, and its expression negatively associated with RSV replication in pHAECs [40,41,42]. In RSV/A2 challenge studies, the mRNA levels were not significantly different among animals previously infected with A2, r19F or r19F CX4C with the exception that r19F CX4C infected animals had lower levels of MX1 mRNA than those from r19F infected animals ( p < 0.01).…”

Protein Arginylation Is Regulated during SARS-CoV-2 Infection

“…Previously published studies were used to verify the abundance of proteins that make up the N-degron pathway in the non-infected and SARS-CoV-2 infected groups: (i) Saccon et al [ 51 ] (Calu-3, Caco-2, Huh7, and 293FT cell lines, proteomics); (ii) Nie et al [ 52 ] (autopsy 7 organs, 19 patients, proteomics); (iii) Leng et al [ 53 ] (lung tissue, 2 patients, proteomics); (iv) Qiu et al [ 54 ] (lung tissue, 3 patients, proteomics); (v) Bojkova et al [ 55 ] (Caco-2 cells, proteomics); (vi) Wu et al [ 56 ] (lung tissue, colonic transcriptomics); and (vii) Desai et al [ 57 ] (lung tissue, transcriptomics). To verify modulation of the N-degron pathway in other viral infections, including MERS-CoV/SARS-CoV/H1N1 influenza virus/Respiratory syncytial virus (RSV), data from the following studies were evaluated: (viii) Zhuravlev et al [ 58 ] (MRC-5, A549, HEK293FT, and WI-38 VA-13 cell lines, H1N1 influenza virus, transcriptomics); (ix) Li et al [ 59 ] (A549 and 293T cell lines, H1N1 influenza virus, transcriptomics); (x) Krishnamoorthy et al [ 60 ] (comparative among coronaviruses, transcriptomics); (xi) Ampuero et al [ 61 ] (time course of RSV infection in the lung, transcriptomics); (xii) Besteman et al [ 62 ] (RSV infected neutrophils, transcriptomics); and (xiii) Dave et al [ 63 ] (RSV infected alveolar cell, proteomics). Deep proteome data from non-infected cell lineages were recently made available publicly by Zecha et al [ 64 ] to model SARS-CoV-2 infection in Vero E6 (kidney epithelial cell, African green monkey), Calu-3 (lung adenocarcinoma), Caco-2 (colorectal adenocarcinoma), and ACE2-A549 (lung carcinoma expressing ACE2 to gain cellular entry).…”