Virus Expression Database

GSE136342

West Nile virus infection of human monocyte-derived dendritic cells

Submitted by Mehul Shamal Suthar (Emory University, USA) on Aug 26 2019

Platform: ngs – Illumina HiSeq 2500 (Homo sapiens)

Pubmed: None listed

Summary West Nile virus (WNV) is a neurotropic flavivirus and the leading cause of mosquito-borne encephalitis in the United States. Recent studies in humans have found that dysfunctional T cell responses strongly correlate with development of severe WNV neuroinvasive disease. However, the contributions of human dendritic cells (DCs) in priming WNV-specific T cell immunity remains poorly understood. Here, we demonstrate that human monocyte derived DCs (moDCs) support productive viral replication following infection with a pathogenic strain of WNV. Antiviral effector gene transcription was strongly induced during the log-phase viral growth, while secretion of type I interferons (IFN) occurred with delayed kinetics. Activation of RIG-I like receptor (RLR) or type I IFN signaling prior to log-phase viral growth significantly diminished viral replication, suggesting that early activation of antiviral programs can block WNV infection. In contrast to the induction of antiviral responses, WNV infection did not promote transcription or secretion of pro-inflammatory (IL-6, GM-CSF, CCL3, CCL5, CXCL9) or T cell modulatory cytokines (IL-4, IL-12, IL-15). There was also minimal induction of molecules associated with antigen presentation and T cell priming, including the co-stimulatory molecules CD80, CD86, and CD40. Functionally, WNV-infected moDCs dampened allogenic CD4 and CD8 T cell activation and proliferation. Combined, we propose a model where WNV subverts human DC activation to compromise priming of WNV-specific T cell immunity.

35 Samples

ID Title Cell Type Timepoint Reported Virus Virus Species Exclusion Reason
GSM4047032 D9_Mock_12H monocyte-derived dendritic cell  12 hrs mock Uninfected
GSM4047033 D9_Mock_24H monocyte-derived dendritic cell  24 hrs mock Uninfected
GSM4047034 D9_WNV_12H monocyte-derived dendritic cell  12 hrs WNV West Nile virus
GSM4047035 D9_WNV_24H monocyte-derived dendritic cell  24 hrs WNV West Nile virus
GSM4047036 D9_RIG-I_12H monocyte-derived dendritic cell  12 hrs none Uninfected Extra interventions
RIG-I agonist
GSM4047037 D9_MDA5_12H monocyte-derived dendritic cell  12 hrs none Uninfected Extra interventions
MDA5 agonist
GSM4047038 D9_IFNb_12H monocyte-derived dendritic cell  12 hrs none Uninfected Extra interventions
IFNb agonist
GSM4047039 D125_Mock_12H monocyte-derived dendritic cell  12 hrs mock Uninfected
GSM4047040 D125_Mock_24H monocyte-derived dendritic cell  24 hrs mock Uninfected
GSM4047041 D125_WNV_12H monocyte-derived dendritic cell  12 hrs WNV West Nile virus
GSM4047042 D125_WNV_24H monocyte-derived dendritic cell  24 hrs WNV West Nile virus
GSM4047043 D125_RIG-I_12H monocyte-derived dendritic cell  12 hrs none Uninfected Extra interventions
RIG-I agonist
GSM4047044 D125_MDA5_12H monocyte-derived dendritic cell  12 hrs none Uninfected Extra interventions
MDA5 agonist
GSM4047045 D125_IFNb_12H monocyte-derived dendritic cell  12 hrs none Uninfected Extra interventions
IFNb agonist
GSM4047046 D253_Mock_12H monocyte-derived dendritic cell  12 hrs mock Uninfected
GSM4047047 D253_Mock_24H monocyte-derived dendritic cell  24 hrs mock Uninfected
GSM4047048 D253_WNV_12H monocyte-derived dendritic cell  12 hrs WNV West Nile virus
GSM4047049 D253_WNV_24H monocyte-derived dendritic cell  24 hrs WNV West Nile virus
GSM4047050 D253_RIG-I_12H monocyte-derived dendritic cell  12 hrs none Uninfected Extra interventions
RIG-I agonist
GSM4047051 D253_MDA5_12H monocyte-derived dendritic cell  12 hrs none Uninfected Extra interventions
MDA5 agonist
GSM4047052 D253_IFNb_12H monocyte-derived dendritic cell  12 hrs none Uninfected Extra interventions
IFNb agonist
GSM4047053 D434_Mock_12H monocyte-derived dendritic cell  12 hrs mock Uninfected
GSM4047054 D434_Mock_24H monocyte-derived dendritic cell  24 hrs mock Uninfected
GSM4047055 D434_WNV_12H monocyte-derived dendritic cell  12 hrs WNV West Nile virus
GSM4047056 D434_WNV_24H monocyte-derived dendritic cell  24 hrs WNV West Nile virus
GSM4047057 D434_RIG-I_12H monocyte-derived dendritic cell  12 hrs none Uninfected Extra interventions
RIG-I agonist
GSM4047058 D434_MDA5_12H monocyte-derived dendritic cell  12 hrs none Uninfected Extra interventions
MDA5 agonist
GSM4047059 D434_IFNb_12H monocyte-derived dendritic cell  12 hrs none Uninfected Extra interventions
IFNb agonist
GSM4047060 D447_Mock_12H monocyte-derived dendritic cell  12 hrs mock Uninfected
GSM4047061 D447_Mock_24H monocyte-derived dendritic cell  24 hrs mock Uninfected
GSM4047062 D447_WNV_12H monocyte-derived dendritic cell  12 hrs WNV West Nile virus
GSM4047063 D447_WNV_24H monocyte-derived dendritic cell  24 hrs WNV West Nile virus
GSM4047064 D447_RIG-I_12H monocyte-derived dendritic cell  12 hrs none Uninfected Extra interventions
RIG-I agonist
GSM4047065 D447_MDA5_12H monocyte-derived dendritic cell  12 hrs none Uninfected Extra interventions
MDA5 agonist
GSM4047066 D447_IFNb_12H monocyte-derived dendritic cell  12 hrs none Uninfected Extra interventions
IFNb agonist