Virus Expression Database

GSE165340

Reduced Nucleoprotein availability impairs negative-sense RNA virus replication and promotes host recognition

Submitted by Daniel Blanco Melo (Icahn School of Medicine at Mount Sina, USA) on Jan 22 2021

Platform: ngs – Illumina NextSeq 500 (Homo sapiens)

Pubmed: 33568513

Summary Negative-sense RNA viruses (NSVs) rely on prepackaged viral RNA-dependent RNA polymerases (RdRp) to replicate and transcribe their viral genomes. Their replication machinery consists of an RdRp bound to viral RNA which is wound around a nucleoprotein (NP) scaffold, forming a viral ribonucleoprotein complex. NSV NP is known to regulate transcription and replication of genomic RNA, however its role in maintaining and protecting the viral genetic material is unknown. Here, we exploited host microRNA expression to target NP of influenza A virus and Sendai virus to ascertain how this would impact genomic levels and the host response to infection. We find that in addition to inducing a drastic decrease in genome replication, the antiviral host response in the absence of NP is dramatically enhanced. Additionally, our data shows that insufficient levels of NP prevent the replication machinery of these NSVs to process full-length genomes, resulting in aberrant replication products which form pathogen-associated molecular patterns in the process. These dynamics facilitate immune recognition by cellular pattern recognition receptors leading to a strong host antiviral response. Moreover, we observe that the consequences of limiting NP levels are universal amongst NSVs including Ebola virus, Lassa virus and Measles virus. Overall, these results provide new insights into viral genome replication of negative-sense RNA viruses and highlight novel avenues towards developing effective antiviral strategies, adjuvants, and/or live-attenuated vaccines.

27 Samples

ID Title Cell Type Timepoint Reported Virus Virus Species Exclusion Reason
GSM5031744 Series1_A549_Mock_1 non-small cell lung adenocarcinoma cell line  [A-549 ] Mock Uninfected
GSM5031745 Series1_A549_Mock_2 non-small cell lung adenocarcinoma cell line  [A-549 ] Mock Uninfected
GSM5031746 Series1_A549_IAV-NC-9h_1 non-small cell lung adenocarcinoma cell line  [A-549 ] 9 hrs IAV Influenza A virus
GSM5031747 Series1_A549_IAV-NC-9h_2 non-small cell lung adenocarcinoma cell line  [A-549 ] 9 hrs IAV Influenza A virus
GSM5031748 Series1_A549_IAV-NT-9h_1 non-small cell lung adenocarcinoma cell line  [A-549 ] 9 hrs IAV Influenza A virus Extra interventions
recombinant virus
GSM5031749 Series1_A549_IAV-NT-9h_2 non-small cell lung adenocarcinoma cell line  [A-549 ] 9 hrs IAV Influenza A virus Extra interventions
recombinant virus
GSM5031750 Series2_A549_Mock_1 (SeV-NC control) non-small cell lung adenocarcinoma cell line  [A-549 ] Mock Uninfected
GSM5031751 Series2_A549_Mock_2 (SeV-NC control) non-small cell lung adenocarcinoma cell line  [A-549 ] Mock Uninfected
GSM5031752 Series2_A549_Mock_3 (SeV-NC control) non-small cell lung adenocarcinoma cell line  [A-549 ] Mock Uninfected
GSM5031753 Series2_A549_SeV-NC-24h_1 non-small cell lung adenocarcinoma cell line  [A-549 ] 24 hrs SeV (Fushimi) Murine respirovirus
GSM5031754 Series2_A549_SeV-NC-24h_2 non-small cell lung adenocarcinoma cell line  [A-549 ] 24 hrs SeV (Fushimi) Murine respirovirus
GSM5031755 Series2_A549_SeV-NT-24h_1 non-small cell lung adenocarcinoma cell line  [A-549 ] 24 hrs SeV (Fushimi) Murine respirovirus Extra interventions
recombinant virus
GSM5031756 Series2_A549_SeV-NT-24h_2 non-small cell lung adenocarcinoma cell line  [A-549 ] 24 hrs SeV (Fushimi) Murine respirovirus Extra interventions
recombinant virus
GSM5031757 Series3_A549_IAV-NC-9h_1 non-small cell lung adenocarcinoma cell line  [A-549 ] 9 hrs IAV Influenza A virus
GSM5031758 Series3_A549_IAV-NC-9h_2 non-small cell lung adenocarcinoma cell line  [A-549 ] 9 hrs IAV Influenza A virus
GSM5031759 Series3_A549_IAV-NT-9h_1 non-small cell lung adenocarcinoma cell line  [A-549 ] 9 hrs IAV Influenza A virus Extra interventions
recombinant virus
GSM5031760 Series3_A549_IAV-NT-9h_2 non-small cell lung adenocarcinoma cell line  [A-549 ] 9 hrs IAV Influenza A virus Extra interventions
recombinant virus
GSM5031761 Series4_A549_SeV-NC-9h_1 non-small cell lung adenocarcinoma cell line  [A-549 ] 24 hrs SeV (Fushimi) Murine respirovirus
GSM5031762 Series4_A549_SeV-NC-9h_2 non-small cell lung adenocarcinoma cell line  [A-549 ] 24 hrs SeV (Fushimi) Murine respirovirus
GSM5031763 Series4_A549_SeV-NT-9h_1 non-small cell lung adenocarcinoma cell line  [A-549 ] 24 hrs SeV (Fushimi) Murine respirovirus Extra interventions
recombinant virus
GSM5031764 Series4_A549_SeV-NT-9h_2 non-small cell lung adenocarcinoma cell line  [A-549 ] 24 hrs SeV (Fushimi) Murine respirovirus Extra interventions
recombinant virus
GSM5031765 Series5_A549ACE2_SARS-CoV-2-siScr-24h_1 non-small cell lung adenocarcinoma cell line  [A-549 ] 24 hrs SARS-CoV-2 Severe acute respiratory syndrome-related coronavirus Extra interventions
ACE2 overexpressed
GSM5031766 Series5_A549ACE2_SARS-CoV-2-siScr-24h_2 non-small cell lung adenocarcinoma cell line  [A-549 ] 24 hrs SARS-CoV-2 Severe acute respiratory syndrome-related coronavirus Extra interventions
ACE2 overexpressed
GSM5031767 Series5_A549ACE2_SARS-CoV-2-siScr-24h_3 non-small cell lung adenocarcinoma cell line  [A-549 ] 24 hrs SARS-CoV-2 Severe acute respiratory syndrome-related coronavirus Extra interventions
ACE2 overexpressed
GSM5031768 Series5_A549ACE2_SARS-CoV-2-siN-24h_1 non-small cell lung adenocarcinoma cell line  [A-549 ] 24 hrs SARS-CoV-2 Severe acute respiratory syndrome-related coronavirus Extra interventions
siRNA treated; ACE2 overexpressed
GSM5031769 Series5_A549ACE2_SARS-CoV-2-siN-24h_2 non-small cell lung adenocarcinoma cell line  [A-549 ] 24 hrs SARS-CoV-2 Severe acute respiratory syndrome-related coronavirus Extra interventions
siRNA treated; ACE2 overexpressed
GSM5031770 Series5_A549ACE2_SARS-CoV-2-siN-24h_3 non-small cell lung adenocarcinoma cell line  [A-549 ] 24 hrs SARS-CoV-2 Severe acute respiratory syndrome-related coronavirus Extra interventions
siRNA treated; ACE2 overexpressed