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