Respiratory syncytial virus reduces STAT3 phosphorylation in human memory CD8 T cells stimulated with IL-21

Abstract

Respiratory syncytial virus (RSV) is a common cause of childhood lower respiratory tract infections. The recent failure of a vaccine candidate based on recombinant F protein underlines the urgent need to better understand the protective human memory immune response against RSV. Signal transducer and activator of transcription 3 (STAT3) protein is a transcription factor that promotes the maturation of the memory CD8 T cell response in cooperation with IL-10 and IL-21. However, the role of STAT3 in the memory CD8 T cell response during RSV infection remains to be elucidated. We found that in infants with bronchiolitis infected with RSV, the expression of STAT3 detected in nasal washes is reduced when compared to that in infants infected by other viruses. In vitro, RSV impairs STAT3 phosphorylation induced by IL-21 in purified human memory CD8 T cells. In addition, RSV decreases granzyme B production by memory CD8 T cells, reducing its cytotoxic activity against RSV-infected epithelial pulmonary cell lines. Together, these data indicate that RSV modulates the IL-21/STAT3 pathway in human memory CD8 T cells, and this could be a mechanism to be further explored to improve the memory response against the infection.

Influenza Virus-Induced Novel miRNAs Regulate the STAT Pathway

“…Transcription factors have the function of either stabilizing (as an activator) or blocking (as a repressor) the binding of RNA polymerase to DNA and result in the direct control of gene expression. Among the transcription factors, Signal Transducers and Activators of Transcription (STAT) family members are known to regulate several viruses, such as, Epstein–Barr virus infection (STAT1), dengue virus (STAT2) [ 11 , 12 ], and Respiratory syncytial virus (STAT3) [ 13 ]. Several DNA and RNA viruses are also known to regulate STAT3.…”

Identification of potential mRNA panels for severe acute respiratory syndrome coronavirus 2 (COVID-19) diagnosis and treatment using microarray dataset and bioinformatics methods

“…Sanders et al ( 2001 ) revealed that NOS2 was down-regulated in rhinovirus infection, but this gene may be involved in development of SARS-CoV-2 infection. The enriched down-regulated genes found in this study include IL10 (Loebbermann et al 2012a , b ), IL13 (Castilow et al 2008 ), IL21 (Antunes et al 2019 ), CCR6 (Shi et al 2017 ), CXCL13 (Alturaiki et al 2018 ), CCL20 (Shi et al 2017 ), IL19 (Ermers et al 2011 ), IL20 (Ermers et al 2011 ), CD40 (Harcourt et al 2003a , b ), IL2 (Noma et al 1996 ), IL3 (Bertrand et al 2015 ), IL4 (Puthothu et al 2006 ), IL9 (Dodd et al 2009 ) and STAT6 (Srinivasa et al 2016) were responsible for progression of respiratory syncytial virus infection, but these genes may be linked with progression of SARS-CoV-2 infection. Many previous studies have confirmed the roles of enriched down-regulated genes such as IL12B (Mueller et al 2004 ), TNFRSF9 (Rodriguez et al 2019 ), TNFRSF14 (Soroosh et al 2014 ), IL17F (Wang et al 2016), CCR8 (Calado et al 2010 ), CCL18 (Malhotra et al 2019 ), CCL22 (Yang et al 2012 ), CXCL11 (Pineda-Tenor et al 2014 ), CX3CL1 (Bertin et al 2014 ), CXCL12 (Durrant et al 2014 ), CCR10 (Nakayama et al 2002 ), IFNA2 (Chen et al 2017), IFNB1 (Gagné et al 2017 ), IL7 (Golden‐Mason et al 2006), IL26 (Miot et al 2015 ), CXCR1 (Xu et al 2016 ), CEBPB (CCAAT enhancer binding protein beta) (Liu et al 2009 ), ETS1 (Posada et al 2000 ), STAT5A (Warby et al 2003 ), THY1 (Lu et al 2011 ), IL16 (Caufour et al 2001 ), HLA-B (Martin et al 2007 ), HLA-C (Apps et al 2013 ), HLA-DPA1 (Wasityastuti et al 2016 ), HLA-DPB1 (Lambert et al 2015 ), HLA-DQA1 (Tibbs et al 1996 ), HLA-DRB1 (Chi et al 2013 ), PSMB10 (Deng et al 2019 ), BCL2 (Zuckerman et al 2001), TOLLIP (toll interacting protein) (Li et al 2016a , b ), VCAM1 (Koraka et al 2004 ), RAG1 (Winkler et al 2017 ), IRF8 (Terry et al …”

Reliability of self-sampling for accurate assessment of respiratory virus viral and immunologic kinetics

“…For RSV and MPV, we demonstrate that an early surge in IFNγ is coupled with elimination of a massive number of infected cells but is insufficient for complete containment of infection, which is achieved several days later concurrent with slower expansion IL-21. Notably, IL-21 has previously been identified as required for RSV elimination in murine models 29-31 In our model, it induces an extremely high death rate of infected cells once above a certain concentration. Larger scale studies may be able to link surges in different cytokines with different respiratory viruses, including SARS CoV-2, and to differentiate severity using these techniques.…”