The Molecular Epidemiological, Inflammation Response And Pathogenesis Of Respiratory Syncytial Virus Infection In Children

Part 1 The molecular epidemiological of respiratory syncytial virusBackground:Respiratory syncytial virus(RSV) infection is the leading cause of acute respiratory tract disease in children less than 5 years old.Methods(1) To analyze the epidemiological of RSV, we collected the seven kinds of respiratory viral antigen detection data of hospitalized children with respiratory tract infections in department of respiration at the First People's Hospital of Chenzhou from January to December 2014.(2) To further understand the molecular properties, nasal swabs(NSs) were collected to investigate the molecular epidemiological of RSV in the epidemic seasons of RSV in 2014 from hospitalized children with RSV infections. And RSV G genes were amplified by reverse transcription polymerase chain reaction(RT-PCR) and sequenced.(3) To understand the clinical characterization of RSV infections, patient demographics and clinical characteristics were collected and analyzed.Results(1) RSV is the most common virus in children with respiratory tract infection, and outbreaks often last from October to May.(2) We identified 64 patients with RSV infections. A recently identified RSV subtype, ON1(n = 13, 20%), NA1(n = 11, 17%),BA9(n = 39, 61%) and GB2(n = 1, 1.6%). ON1, NA1 and BA9 are dominant strains in children with respiratory tract infections(RTIs).(3) RSV subtypes NA1 and BA9 infections mostly infect infants(<6 months old), however subtype ON1 infections show equal age distribution trends.(4) Phylogenetic analysis indicated that all ON1 and most NA1 isolates lost one potential N-glycosylation site at amino acid 251 and 249 due to T251 K and N249 Y substitution, respectively.(5) RSV mostly causes lower respiratory tract infections(LRTIs)(98.4%) with coughing(100%), sputum production, fever, and wheezing.Conclusions(1) RSV is the leading cause of inducing lower respiratory tract infections in children,and NA1, ON1 and BA9 were the dominants subtypes.(2) Subtype ON1 becomes the predominant subtype. Part 2 Respiratory Syncytial Virus Infection Induced Inflammation Response and Pathogenesis AbstractBackgroundThe inhibitory cytokines with broad immunosuppressive functions involved in regulation of host immune response against virus infection. However, their effects in children with respiratory syncytial virus(RSV) infection have not been illuminated yet.MethodsTo explore the role of inhibitory cytokines in RSV infection, total 99 RSV infected hospitalized children which were distributed into three age groups: group?(age ? 6 months), group?(6<age?12 months) and group ?(age >12 months), and 20 age-matched healthy controls were enrolled. Multiple cytokines including T Helper Type 1(Th1) cytokines, including interferon(IFN)-?, interleukin(IL)-2, tumor necrosis factor(TNF) –?; T Helper Type 2(Th2) cytokines, including IL-4, IL-13; T Helper Type 17(Th17) cytokines(IL-17) and inhibitory cytokines including IL-10, IL-27, IL-35 and transforming growth factor(TGF)-? were measured in RSV infected patients and healthy controls plasma by Bio-Plex immunoassay or enzyme linked immunosorbent assay(ELISA).Results(1) The age distribution of RSV patients showed that 43(43.4%) of the patients were age ?6 months, 33(33.3%) were 6 <age ?12 months, 23(23.2%) were age >12 months.(2) We also compared the course of disease between three age groups, and the course of disease were significantly descending in patients age >12 months old, comparing with patients ?6 months old and 6<age?12 months old(P =0.004 and 0.019, respectively).(3) The levels of IL-10 and IL-35 were significantly increased in RSV-infected patients than healthy controls(P =0.006 and P<0.001, respectively). No statistically differences were found in IL-27 and TGF-? expression level in two groups.(4) There are no differences of Th1, Th2 and Th17 cytokines expression comparing with healthy controls.(5) RSV induced IL-10, IL-27 and IL-35 expression increased in an age-dependent manner which inversely parallel with course of disease.(6) And inhibitory cytokine IL-10, negatively correlate with RSV course of disease(r=-0.311, P=0.019).Conclusion(1) Taken together, these data suggested that inhibitory cytokines IL-10, IL-35 and IL-27 play a beneficial role in RSV infection, which can delay the progression of the disease, shorten the course of disease and regulate the balance of immune response.(2) High IL-10 expression is one of critical factors which impact disease progression in RSV infected hospitalization children.