Virus Expression Database

GSE99298

Structural basis for human respiratory syncytial virus NS1-mediated modulation of host responses

Submitted by Maxim N Artyomov (Washington University in St Louis, USA) on May 25 2017

Platform: ngs – Illumina HiSeq 2500 (Homo sapiens)

Pubmed: 28665409

Summary Human respiratory syncytial virus (hRSV) is a major cause of morbidity and mortality in the pediatric, elderly, and immune compromised populations. A gap in our understanding of hRSVdisease pathology is the interplay between virally encoded immune antagonists and host components that limit hRSV replication. hRSV encodes for non-structural (NS) proteins that are important immune antagonists; however, the role of these proteins in viral pathogenesis is incompletely understood. Here we report the crystal structure of hRSV NS1 protein, which suggests that NS1 is a structural paralog of hRSV matrix (M) protein. Comparative analysis of the shared structural fold with M revealed regions unique to NS1. Studies on NS1 WT or mutant alone or in recombinant RSVs demonstrate that structural regions unique to NS1 contribute to modulation of host responses, including inhibition of type I IFN responses, suppression of dendritic cell maturation, and promotion of inflammatory responses. Transcriptional profiles of A549 cells infected with recombinant RSVs show significant differences in multiple host pathways, suggesting that NS1 may have a greater role in regulating host responses than previously appreciated. These results provide a framework to target NS1 for therapeutic development to limit hRSV associated morbidity and mortality.

12 Samples

ID Title Cell Type Timepoint Reported Virus Virus Species Exclusion Reason
GSM2640632 mock_rep1 non-small cell lung adenocarcinoma cell line  [A-549 ] 96 hrs mock Uninfected
GSM2640633 mock_rep2 non-small cell lung adenocarcinoma cell line  [A-549 ] 96 hrs mock Uninfected
GSM2640634 NS1_WT_rep1 non-small cell lung adenocarcinoma cell line  [A-549 ] 96 hrs hRSV Human orthopneumovirus
GSM2640635 NS1_WT_rep2 non-small cell lung adenocarcinoma cell line  [A-549 ] 96 hrs hRSV Human orthopneumovirus
GSM2640636 NS1_WT_rep3 non-small cell lung adenocarcinoma cell line  [A-549 ] 96 hrs hRSV Human orthopneumovirus
GSM2640637 NS1_1_118_rep1 non-small cell lung adenocarcinoma cell line  [A-549 ] 96 hrs hRSV Human orthopneumovirus Extra interventions
mutant RSV
GSM2640638 NS1_1_118_rep2 non-small cell lung adenocarcinoma cell line  [A-549 ] 96 hrs hRSV Human orthopneumovirus Extra interventions
mutant RSV
GSM2640639 NS1_1_118_rep3 non-small cell lung adenocarcinoma cell line  [A-549 ] 96 hrs hRSV Human orthopneumovirus Extra interventions
mutant RSV
GSM2640640 NS1_L132A_L133A_rep1 non-small cell lung adenocarcinoma cell line  [A-549 ] 96 hrs hRSV Human orthopneumovirus Extra interventions
mutant RSV
GSM2640641 NS1_L132A_L133A_rep2 non-small cell lung adenocarcinoma cell line  [A-549 ] 96 hrs hRSV Human orthopneumovirus Extra interventions
mutant RSV
GSM2640642 NS1_Y125A_rep1 non-small cell lung adenocarcinoma cell line  [A-549 ] 96 hrs hRSV Human orthopneumovirus Extra interventions
mutant RSV
GSM2640643 NS1_Y125A_rep2 non-small cell lung adenocarcinoma cell line  [A-549 ] 96 hrs hRSV Human orthopneumovirus Extra interventions
mutant RSV