Gene signature of children with severe respiratory syncytial virus infection

Abstract

Background The limited treatment options for children with severe respiratory syncytial virus (RSV) infection highlights the need for a comprehensive understanding of the host cellular response during infection. We aimed to identify host genes that are associated with severe RSV disease and to identify drugs that can be repurposed for the treatment of severe RSV infection. Methods We examined clinical data and blood samples from 37 hospitalized children (29 mild and 8 severe) with RSV infection. We tested RNA from blood samples using next-generation sequencing to profile global mRNA expression and identify cellular processes. Results Retractions, decreased breath sounds, and tachypnea were associated with disease severity. We observed upregulation of genes related to neutrophil, inflammatory response, blood coagulation, and downregulation of genes related to T cell response in children with severe RSV. Using network-based approach, 43 drugs were identified that are predicted to interact with the gene products of these differentially expressed genes. Conclusions These results suggest that the changes in the expression pattern in the innate and adaptive immune responses may be associated with RSV clinical severity. Compounds that target these cellular processes can be repositioned as candidate drugs in the treatment of severe RSV. Impact Neutrophil, inflammation, and blood coagulation genes are upregulated in children with severe RSV infection. Expression of T cell response genes are suppressed in cases of severe RSV. Genes identified in this study can contribute in understanding the pathogenesis of RSV disease severity. Drugs that target cellular processes associated with severe RSV can be repositioned as potential therapeutic options.

Decreased human respiratory syncytial virus activity during the COVID-19 pandemic in Japan: an ecological time-series analysis

“…Unlike for seasonal influenza, no licensed prophylactic vaccine has been developed and supplied to date for HRSV. With regards to drugs targeted against HRSV, palivizumab (anti-HRSV antibody), the humanized monoclonal antibody to HRSV fusion (F) protein, is currently limited to passive vaccination for the prevention of severe disease [ 2 , 53 , 54 ]. Therefore, as a vaccine has not yet been developed, thorough hand hygiene can be an important intervention to reduce person-to-person transmission of HRSV, thus preventing an epidemic.…”

Interactomics: Dozens of Viruses, Co-evolving With Humans, Including the Influenza A Virus, may Actively Distort Human Aging

“…Moreover, we used published transcriptomic data to further investigate the potential of several top age-distorter candidates to interfere with cellular senescence. We took advantage of the recent demonstration that human cellular senescence can be empirically deduced from transcriptomes through differential expression of a set of 125 biomarker genes, known as SenMayo biomarkers ( Saul et al 2022 ), to search for evidence of an alteration of cellular senescence associated with various viral infection ( Kaczkowski et al 2012 ; Jagya et al 2014 ; Peng et al 2014 ; Bercovich-Kinori et al 2016 ; Devadas et al 2016 ; Hu et al 2016 ; Tang et al 2016 ; Zhang et al 2016 ; Boldanova et al 2017 ; Deshiere et al 2017 ; Harden et al 2017 ; Hojka-Osinska et al 2017 ; Klymenko et al 2017 ; McGrath et al 2017 ; Oberstein and Shenk 2017 ; Oh et al 2017 ; Razooky et al 2017 ; Viollet et al 2017 ; Zhu et al 2017 ; Journo et al 2018 ; Tso et al 2018 ; Golumbeanu et al 2019 ; Mrozek-Gorska et al 2019 ; Wang et al 2019 ; Blanco-Melo et al 2020 ; Dissanayake et al 2020 ; Li et al 2020 ; Seelbinder et al 2020 ; Sen et al 2020 ; Sheng et al 2020 ; Thompson et al 2020 ; Winer et al 2020 ; Zhuravlev et al 2020 ; Bauby et al 2021 ; Chandrashekar et al 2021 ; Chow et al 2021 ; Coelho et al 2021 ; Dapat et al 2021 ; van der Heijden et al 2021 ; Hong et al 2021 ; Tegtmeyer et al 2021 ; Tsalik et al 2021 ; Yanagi et al 2021 ; Yuan et a...…”

Exploring Key Genes and Mechanisms in Respiratory Syncytial Virus-Infected BALB/c Mice via Multi-Organ Expression Profiles

“…Compared with girls, boys were reported to have a higher incidence of bronchiolitis with higher activated platelets ( De Jacobis et al., 2020 ). In addition, genes related to platelets were up-regulated in children with severe RSV infection ( Dapat et al., 2021 ). In COVID-19 patients, platelet degranulation may serve as a biomarker for disease severity ( Shen et al., 2020 ) and platelet degranulation dysfunction was closely related with illness severity ( Shu et al., 2020 ).…”

“…Several factors have been identified as critical to the pathogenesis of RSV infection, including systemic innate immune response, inflammatory response, coagulation activation, T cell associated immune response, and viral factors, such as viral load and specific RSV genotype ( Hasegawa et al., 2015 ; Heinonen et al., 2020 ; Dapat et al., 2021 ). However, most previous studies have concentrated on the effects of RSV on lungs and blood, and a comprehensive understanding of RSV pathogenesis from a more systematic perspective is lacking.…”