Predominance of A2063G mutant strains in the Mycoplasma pneumoniae epidemic in children: A clinical and epidemiological study in 2023 in Wuhan, China.

OBJECTIVES: The prevalence of respiratory infectious diseases has changed in the post-COVID-19 epidemic era, and mycoplasma pneumoniae (MP) infection in children has attracted wide attention. METHODS: Children hospitalized for pneumonia in Wuhan, China, in 2023 were enrolled. Respiratory secretions were obtained for the targeted next-generation sequencing (tNGS) including mutation of MP. Pulmonary inflammation was divided into bronchopneumonia and pulmonary consolidation/atelectasis according to lung computed tomography imaging. RESULTS: Of the 667 pediatric pneumonia, 478 were MP positive (72%). The positive rate of MP detected by tNGS increased from April, and MP had become the primary pathogen of pneumonia in children in 2023. The 23S rRNA mutations were all A2063G, accounting for 85% of detected MP. The clinical symptoms of the mutant and wild-type strains were similar, with half of them experiencing atelectasis and lung consolidation. Early bronchoscopic lavage combined with azithromycin in pediatric pulmonary consolidation was an effective therapy strategy, which could be an alternative selection to MP pneumonia treatment. CONCLUSIONS: A2063G mutant strain MP was the primary pathogen of mycoplasma pneumoniae in children recently, which was often complicated by extra-pulmonary symptoms and complications.

A novel porous hydroxyapatite scaffold (pHAMG) enhances angiogenesis and osteogenesis around dental implants by regulating the immune microenvironment.

OBJECTIVE: The purpose was to evaluate whether a novel porous hydroxyapatite (HA) scaffold with a 25-30-µm groove structure (pHAMG) may improve bone osteogenesis, angiogenesis, and bone integration of titanium dental implants in animal models. METHODS: The pHAMG was prepared by chemical precipitation method and its elemental composition and crystal structure were evaluated. The ability of the scaffolds to induce ectopic osteogenesis and the ability of scaffolds combined with titanium dental implants to induce orthotopic peri-implant angiogenesis, osteogenesis, and osteointegration were tested after implantation into the femur muscle pocket in rats and the mandibular defects in beagle dogs, respectively. The elemental composition was evaluated by SEM-EDS; the expression of the relevant osteogenic/inflammation marker and the anti-/pro-inflammation markers was evaluated by immunostaining and immunofluorescence, respectively. RESULTS: In animal experiments with ectopic and peri-implant osteogenesis, pHAMG resulted in significantly larger neovascularization by hematoxylin-eosin staining, as well as deposition of collagen fibers by Masson staining than HA. Meanwhile, microgrooves in pHAMG upregulate more bone morphogenetic protein (BMP) 2 and interleukin-4 (IL-4) and -10 (IL-10) and downregulate more IL-1ß and tumor necrosis factor-α (TNF-α) than that in HA. The pHAMG showed greater expression of arginase (Arg)-1 and lower expression of inducible nitric oxide synthase (iNOS) than HA. CONCLUSION: The novel pHAMG can better repair bone defects in ectopic and orthotopic model. It also transfers macrophages to anti-inflammatory phenotypes, promoting angiogenic and osteogenesis in scaffolds, and bone integration in implants. CLINICAL RELEVANCE: The novel pHAMG induce greater osteogenesis and angiogenesis which could be utilized in the clinical treatment.

Alveolar macrophages and airway hyperresponsiveness associated with respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is a ubiquitous pathogen of viral bronchiolitis and pneumonia in children younger than 2 years of age, which is closely associated with recurrent wheezing and airway hyperresponsiveness (AHR). Alveolar macrophages (AMs) located on the surface of the alveoli cavity are the important innate immune barrier in the respiratory tract. AMs are recognized as recruited airspace macrophages (RecAMs) and resident airspace macrophages (RAMs) based on their origins and roaming traits. AMs are polarized in the case of RSV infection, forming two macrophage phenotypes termed as M1-like and M2-like macrophages. Both M1 macrophages and M2 macrophages are involved in the modulation of inflammatory responses, among which M1 macrophages are capable of pro-inflammatory responses and M2 macrophages are capable of anti-proinflammatory responses and repair damaged tissues in the acute and convalescent phases of RSV infection. Polarized AMs affect disease progression through the alteration of immune cell surface phenotypes as well as participate in the regulation of T lymphocyte differentiation and the type of inflammatory response, which are closely associated with long-term AHR. In recent years, some progress have been made in the regulatory mechanism of AM polarization caused by RSV infection, which participates in acute respiratory inflammatory response and mediating AHR in infants. Here we summarized the role of RSV-infection-mediated AM polarization associated with AHR in infants.

Comparison of short-term efficacy of MIS-TLIF and Endo-LIF in the treatment of single-segment degenerative lumbar diseases.

Background: A prospective controlled study was conducted to compare the short-term clinical results and postoperative complications of minimally invasive transforaminal lumbar decompression and fusion (minimally invasive surgery transforaminal lumbar interbody fusion, MIS-TLIF) and percutaneous endoscope-assisted transforaminal lumbar interbody fusion (endoscopic lumbar interbody fusion, Endo-LIF) in the treatment of single-segment degenerative lumbar diseases, to provide some scientific guidance for clinicians to select surgical treatment for patients with lumbar degeneration. Methods: From October 2020 to October 2021, a total of 62 patients were enrolled, with 31 patients in the MIS-TLIF group and 31 patients in the Endo-LIF group. All patients were followed up for 6 months. The following information from the two groups of patients was recorded: (1) operation time, radiation exposure time, intraoperative blood loss, bed rest time, and hospital stay; (2) ODI score (The Oswestry Disability Index), low back pain VAS score (Visual Analogue Scale), and lumbar vertebra JOA score (Japanese Orthopaedic Association Scores) 1 day before the operation; 1, 3, 6 days after operation; and 1, 3 and 6 months after operation. (3) X-ray evaluations of lumbar fusion at the last follow-up. Results: There were significant differences in operation time, intraoperative fluoroscopy time, and hospitalization cost between the two groups. The MIS-TLIF group was significantly better than the Endo-LIF group, and the intraoperative bleeding volume of the Endo-LIF group was significantly better than that of the MIS-TLIF group, but there was no significant difference in postoperative bed rest time and postoperative hospital stay. There was no significant difference in the scores of ODI, VAS, and JOA between the two groups before and after the operation. At the last follow-up, the fusion rate was 100% in the MIS-TLIF group and 100% in the Endo-LIF group. Conclusions: There was no significant difference in short-term clinical efficacy and safety between Endo-LIF and MIS-TLIF in the treatment of single-segment degenerative lumbar diseases, but MIS-TLIF was significantly better than Endo-LIF in terms of the operation time, hospitalization cost, and fluoroscopy time, and Endo-LIF was significantly better than MIS-TLIF in terms of intraoperative blood loss.

Human Parvovirus B19 Nonstructural Protein 1 Regulates GATA1 Expression via the Notch Signaling Pathway in K562 Cell Line.

BACKGROUND: Human parvovirus B19 (B19) infection can affect the hematopoietic arrest in fetus by hindering the differentiation and maturation of erythroid progenitor cells. B19 nonstructural protein 1 (NS1) has been shown to inhibit the differentiation of erythroid progenitor cells. The goal of this study is to explore the role of B19 NS1 in the regulation of GATA1 and Notch signaling pathway in hematopoietic cells. METHODS: The B19 NS1 expression plasmid was reconstituted, and the possibility of NS1 regulating GATA1 and GATA2 expression modulated by Notch-Hes pathway was tested by qRT-PCR and western blot. Immunofluorescence assays were conducted to visualize pNS1 in K562 cells. RESULTS: We demonstrate that B19 NS1 inhibited GATA1 and induced Hes1/Hes5, which is involved in the activation of Notch signaling pathway. Meanwhile, NS1 exhibited promoting effects on GATA2 expression. Activation of the Notch signaling pathway up-regulated its downstream transcriptional repressor family Hes, thereby inhibiting the expression of GATA gene in K562 cells. CONCLUSIONS: The results show that B19 NS1 protein negatively regulates GATA1 related nuclear transcription and may interfere with hematopoietic cell differentiation.

Diagnostic values of 2 different techniques for controversial lumbar disc herniation by conventional imaging examination: 3D-DESS vs. CT plain scan.

Background: The aim of this study was to explore the significance of three-dimensional double-echo steady-state (3D-DESS) sequence and multidetector computed tomography (CT) plain scan in the diagnosis of lumbar disc herniation (LDH) remaining controversial in conventional magnetic resonance imaging (MRI), and to compare the efficiency between 3D-DESS and CT in diagnosing controversial patients by conventional MRI. Methods: A total of 61 patients with controversial LDH diagnosed by conventional MRI were collected. Before operation, the disease of these patients was further confirmed by 3D-DESS sequences and continuous CT plain scan from L3 to S1. Finally, for patients whose postoperative curative effect was marked and symptoms were obviously alleviated, the sensitivity, specificity and accuracy. Results: Among, 59 patients with remarkably relieved symptoms after operation were included, and 2 patients with varying degrees of non-remission of pain and partial dysfunction after operation were excluded. The sensitivity, specificity and accuracy of 3D-DESS were 94.6, 100 and 94.9%, respectively, and those of CT were 75.0, 33.3 and 72.9%, respectively. Conclusion: 3D-DESS is a very useful diagnostic method for patients with some special types of LDH that remain controversial in conventional imaging diagnostic methods. Through 3D-DESS, the morphology of lumbosacral nerve roots can be directly observed, which is conducive to the improvement of the sensitivity, specificity and accuracy, thus further reducing the misdiagnosis rate. Moreover, 3D-DESS plays a guiding role in the formulation of operative methods.

Respiratory Syncytial Virus Nonstructural Protein 1 Promotes 5-Lipoxygenase via miR-19a-3p.

Background: Respiratory syncytial virus (RSV) infection can regulate the expression of a wide range of noncoding microRNAs (miRNAs), in which mir-19a-3p can participate in airway inflammatory response by regulating 5-lipoxygenase (5-LO) pathway. RSV nonstructural protein (NS) 1 is involved in the airway hyperresponsiveness during RSV infection. Methods: The expression levels of miR-19a-3p and inflammatory signaling-related indicators were detected using quantitative real-time PCR and western blot analyses on the A549 cells transfected with NS1 expression plasmids (pNS1). The 5-LO-mediated inflammatory signaling pathway was assessed when the miR-19a-3p or 5-LO was inhibited. Results: The immunofluorescence analysis showed that the plasmid-mediated NS1 protein was observed in both the cytoplasm and nucleus. The expression level of miR-19a-3p was significantly upregulated in the pNS1 or RSV-treated cells, which was reversed by the NS1 small interfering RNA. In addition, pNS1 also upregulated the expression of 5-LO, interleukin-5 (IL-5), and leukotriene B4 (LTB4), which was also significantly inhibited by the miR-19a-3p antagonists. The 5-LO inhibitor MK886 prevented the increase in the expression level of IL-5 induced by pNS1. Conclusions: These results suggested that the RSV NS1 might play an important role in the pathogenesis of RSV by activating the 5-LO and subsequent inflammatory cytokines through miR-19a-3p.

Metabolomics Characterize the Differential Metabolic Markers between Bama Xiang Pig and Debao Pig to Identify Pork.

The Bama Xiang pig (BM) is a unique pig species in Guangxi Province, China. Compared to other breeds of domestic pig, such as the Debao pig (DB), it is smaller in size, better in meat quality, resistant to rough feeding and strong in stress resistance. These unique advantages of Bama Xiang pigs make them of great edible value and scientific research value. However, the differences in muscle metabolites between Bama Xiang pigs (BM) and Debao pigs (DB) are largely unexplored. Here, we identified 214 differential metabolites between these two pig breeds by LC-MS. Forty-one such metabolites are enriched into metabolic pathways, and these metabolites correspond to 11 metabolic pathways with significant differences. In Bama pigs, the abundance of various metabolites such as creatine, citric acid, L-valine and hypoxanthine is significantly higher than in Debao pigs, while the abundance of other metabolites, such as carnosine, is significantly lower. Among these, we propose six differential metabolites: L-proline, citric acid, ribose 1-phosphate, L-valine, creatine, and L-arginine, as well as four potential differential metabolites (without the KEGG pathway), alanyl-histidine, inosine 2'-phosphate, oleoylcarnitine, and histidinyl hydroxyproline, as features for evaluating the meat quality of Bama pigs and for differentiating pork from Bama pigs and Debao pigs. This study provides a proof-of-concept example of distinguishing pork from different pig breeds at the metabolite level and sheds light on elucidating the biological processes underlying meat quality differences. Our pork metabolites data are also of great value to the genomics breeding community in meat quality improvement.

Dynamic changes of acquired maternal SARS-CoV-2 IgG in infants.

At present, there are still ambiguous reports about the perinatal infection of infants born to mothers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The dynamic characteristics of infantile serum antibodies born to mother with SARS-CoV-2 has not been well described. In this study, we analyzed the seroconversion of 27 newborns born to 26 pregnant women infected with SARS-CoV-2. The SARS-CoV-2 IgG positive rate of parturient was 80.8%, and half of their infants obtained maternal IgG. IgG transfer rates were 18.8% and 81.8% in those infants whose mother infected less and more than 2 weeks before delivery. In the first two months of life, the IgG level of infants dropped sharply to one tenth of that at birth. These results suggest that maternal SARS-CoV-2 IgG provides limited protection for infants.

Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer.

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan-Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

New Insights of Human Parvovirus B19 in Modulating Erythroid Progenitor Cell Differentiation.

Human parvovirus B19 (B19), a human pathogen of the erythroparvovirus genus, is responsible for a variety of diseases. B19 cause less symptoms in healthy individuals, also cause acute and chronic anemia in immunodeficiency patients. Transient aplastic crisis and pure red cell aplasia are two kinds of anemic hemogram, respectively, in acute and chronic B19 infection phase, especially occurring in patients with a shortened red cell survival or with immunodeficiency. In addition, B19-infected pregnant women may cause hydrops fetalis or fetal loss. B19 possesses high affinity to bone marrow and fetal liver due to its extremely restricted cytotoxicity to erythroid progenitor cells (EPCs) mediated by viral proteins. The nonstructural protein NS1 is considered to be the major pathogenic factor, which has been shown to inhibit the differentiation and maturation of EPCs through inducing viral DNA damage responses and cell cycle arrest. The time phase property of NS1 activity during DNA replication and conformity to transient change of hemogram are suggestive of its role in regulating differentiation of hematopoietic cells, which is not completely understood. In this review, we summarized the bridge between B19 NS1 and Notch signaling pathway or transcriptional factors GATA, which play an important role in erythroid cell proliferation and differentiation, to provide a new insight of the potential mechanism of B19-induced differential inhibition of EPCs.

The immunologic status of newborns born to SARS-CoV-2-infected mothers in Wuhan, China.

BACKGROUND: Immunologic dysfunction due to coronavirus disease 2019 (COVID-19) is closely related to clinical prognosis, and the inflammatory response of pregnant women may affect the directional differentiation and function of fetal immune cells. OBJECTIVE: We sought to analyze the immune status of newborns from mothers with COVID-19 in the third trimester. METHODS: Along with collecting the clinical data from 51 newborns and their respective mothers, we recorded the immunophenotypes and cytokine and immunoglobulin levels of the newborns. RESULTS: None of the 51 newborns showed fever or respiratory distress during hospitalization. Detection of severe acute respiratory syndrome coronavirus 2 nucleic acid in pharyngeal swabs was negative. Except for the low level of CD16-CD56 cells, the count and proportion of lymphocytes, CD3, CD4, CD8, and CD19 were all in the normal range. Moreover, the serum IgG and IgM levels were within the normal range, whereas IL-6 showed increased levels. There was no correlation between maternal COVID-19 duration and the lymphocyte subsets or cytokine levels (IFN-γ, IL-2, IL-4, IL-6, IL-10, and TNF-α). There was a positive correlation between IL-6 and IL-10 levels and CD16-CD56 cells. One (1.96%) infant with an extremely elevated IL-6 concentration developed necrotizing enterocolitis in the third week after birth, and the remaining 50 infants did not show abnormal symptoms through the end of the follow-up period. CONCLUSIONS: COVID-19 in the third trimester did not significantly affect the cellular and humoral immunity of the fetus, and there was no evidence that the differentiation of lymphocyte subsets was seriously unbalanced.

Clinical characteristics and risk assessment of newborns born to mothers with COVID-19.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is causing an outbreak of pneumonia in Wuhan, Hubei Province, China, and other international areas. OBJECTIVE: Here, we report the clinical characteristics of the newborns delivered by SARS-CoV-2 infected pregnant women. METHODS: We prospectively collected and analyzed the clinical features, laboratory data and outcomes of 7 newborns delivered by SARS-CoV-2 infected pregnant women in Zhongnan Hospital of Wuhan University during January 20 to January 29, 2020. RESULTS: 4 of the 7 newborns were late preterm with gestational age between 36 weeks and 37 weeks, and the other 3 were full-term infants. The average birth weight was 2096 ± 660 g. All newborns were born without asphyxia. 2 premature infants performed mild grunting after birth, but relieved rapidly with non-invasive continuous positive airway pressure (nCPAP) ventilation. 3 cases had chest X-ray, 1 was normal and 2 who were supported by nCPAP presented mild neonatal respiratory distress syndrome (NRDS). Samples of pharyngeal swab in 6 cases, amniotic fluid and umbilical cord blood in 4 cases were tested by qRT-PCR, and there was no positive result of SARS-CoV-2 nucleic acid in all cases. CONCLUSIONS: The current data show that the infection of SARS-CoV-2 in late pregnant women does not cause adverse outcomes in their newborns, however, it is necessary to separate newborns from mothers immediately to avoid the potential threats.

Phototherapy is associated with the decrease in serum globulin levels in neonatal hyperbilirubinemia.

Previous studies have indicated that phototherapy may be associated with childhood immune disorders in later life. The present study aimed to assess the effects of phototherapy as a risk factor in the decrease in serum globulin (GLB) levels during neonatal hyperbilirubinemia. A total of 430 full-term infants aged between 1 and 28 days, diagnosed with neonatal hyperbilirubinemia, were enrolled in the present study. Neonates with intrauterine infection, genetic abnormalities and congenital diseases were excluded from the cohort. All neonates received single-side phototherapy (halogen lamps for 12 h per day, for 3 days) and/or intravenous albumin (IVALB; 1 g/kg/day, for 2 days) and/or intravenous immunoglobulin (1 g/kg/day, for 2 days). Total serum bilirubin (TSB), albumin (ALB) and GLB levels were examined twice, on the first and fourth days of hospitalization. Neonatal TSB concentrations decreased from 299.6±83.9 to 163.6±57.6 µmol/l following 3 days of intensive treatment (P<0.001). Pearson correlative analysis indicated that TSB was significantly correlated to the GLB level (r=0.249; P<0.01), but not with ALB level. There was a significant decrease in GLB levels following phototherapy+IVALB (P<0.001). The GLB levels decreased to 2-4 g/l (10-20% compared with their baseline levels) and were markedly decreased in infants >16 days old compared with those in patients aged <16 days (P<0.001). The decreases in GLB levels observed were 21.3±4.1 to 18.5±4.2 g/l in the phototherapy group, and 23.0±3.9 to 16.6±4.5 g/l in the phototherapy+IVALB (P<0.001). The decrease in GLB levels was associated with age (95% confidence interval; -0.152, -0.016). The results demonstrated that phototherapy decreased serum GLB levels, particularly in infants aged >16 days, while additional IVALB treatment promoted the decrease, along with increased age.

MicroRNAs: Mediators and Therapeutic Targets to Airway Hyper Reactivity After Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is the most important pathogen correlated to the first-time infant wheezing and later recurrence after its primary infection. RSV infection promotes the bronchial smooth muscle sensitivity to leukotrienes (LTs) in acute stage, causes the extensive inflammatory reaction and the aggregation of Th2-like cells during respiratory tract obstruction. Infants and young children infected with RSV exhibit an increased susceptibility to the exposure of exogenous allergens, easy to suffer from the recurrent wheezing, which prompts that the body is still in a state of inflammation or immunological bias. However, the pathological mechanism is unclear. The recent researches demonstrate that abnormal expression of non-coding microRNAs (miRNAs) can be detected from the peripheral blood and airway tract epithelial of RSV infected infants, which participate the regulation of immune cells polarization and LTs synthesis. Improving the immune tolerance can significantly relieve the airway inflammation and broncho-spasm caused by RSV. In this review, we discuss recent advances in understanding the mechanism of RSV-induced inflammatory reaction and immune dysfunction leading to airway hyper-reactivity. Further, we summarize the potential molecular basis that, in this process, miRNAs, which are produced by airway epithelial cells or peripheral blood mononuclear cells, directly or in the form of exosome to regulate the inflammation programs as well as the function, differentiation and proliferation of immune cells. miRNAs may become a potential bio-marker of detecting severe RSV infection and a novel target of early intervention and therapeutic strategy in recurrent wheezing or asthma related to RSV infection.

Assessment of neonatal brain volume and growth at different postmenstrual ages by conventional MRI.

Data regarding neonatal brain volumes represent a basis for monitoring early brain development, and large sample of neonatal brain volume data has not been well described. This study was focused on neonatal brain volumes at different postmenstrual ages (PMA) and postnatal age (PNA).A cohort of 415 neonates with PMA 30 to 43 weeks were recruited for the determination of brain volumes. Intracranial cavity (ICC), total brain tissue (TBT), and cerebrospinal fluid (CSF) were evaluated on the basis of T1-weighted sagittal plane magnetic resonance images. Brain magnetic resonance imaging was assessed using maturation scoring system and multiple linear regression analysis was conducted to forecast the effect factors of brain volumes.TBT volume reached a peak growth at 39 to 40 weeks, ICC volume presented peak growth later at around 43 to 44 weeks, and CSF had a cliff fallen at 37 to 38 weeks PMA at scan. The maturation score increased along with PMA, and the TBT and CSF volumes were significantly different between higher and lower gestational age (GA) groups. The ICC and TBT volumes in higher GA group were larger than lower GA group. Most infants in higher GA group had higher TMS than those in lower GA group. Gender, PMA, PNA, and birth weight were predictors of TBT and ICC volumes.Our results showed that premature volumes of ICC and TBT enlarged with the increasing PMA, while volumes of CSF decreased at 37 weeks. Premature earlier to leave the uterus can lead to brain mature retard although they had the same GA compared with those later birth neonates.

High-dose of intravenous immunoglobulin modulates immune tolerance in premature infants.

BACKGROUND: Intravenous immunoglobulin (IVIG) is commonly used to improve the immunomodulatory effects, although its regulatory effect on premature Treg cells is unclear. The purpose of this study is to study the effect of high dose of IVIG (HD-IVIG) on Treg cells expression and cytokine profile in premature birth. METHODS: Fifty-two premature infants were enrolled in this study and thirty-one premature infants who were suspected to have intrauterine infection received HD-IVIG (1-2 g/kg) at the first day of birth; the remaining 21 premature infants were assigned as the control group. The peripheral blood CD4 + T and foxp3+ Treg cells were checked by flow cytometry, and cytokine concentrations were detected by cytometric bead array. RESULTS: With the gestational age growth, peripheral blood CD4 + T and foxp3+ Treg cells of prematurity gradually declined from 50% to 35% and from 8% to 6%, respectively. Meanwhile, HD-IVIG increased the percentage of CD4 + T and foxp3+ Treg cells compared with their baseline levels (p < 0.001). HD-IVIG demonstrated different regulating effects on cytokines secretion, increased IL-17 and TGF-ß, and inhibited IL-6 secretion. CONCLUSION: Our results demonstrated that HD-IVIG not only enhanced the premature immune tolerance, but also suppressed the excessive inflammation response mediated by IL-6. TRIAL REGISTRATION: This study was under the clinical study registration (ChiCTR-ORC-16008872, date of registration, 2016-07-21).

Peripheral blood microRNAs expression is associated with infant respiratory syncytial virus infection.

MicroRNAs respond to the inflammatory responses induced by RNA virus infection. In this study, we investigated the specific microRNA profile in the peripheral blood of infants infected with respiratory syncytial virus (RSV). Blood specimens were analyzed using microRNA microarrays, followed by quantitative RT-PCR. A specific microRNA profile in the peripheral blood of RSV-infected infants was identified for the first time. MiR-106b-5p, miR-20b-5p, and miR-342-3p were upregulated, while miR-320e, miR-320d, miR-877-5p, miR-122-5p, and miR-92b-5p were downregulated. Pathway analysis indicated that the dysregulated microRNAs were involved in inflammatory and immune responses, including Wnt, TGF-ß, insulin, and T and B cell receptor signaling. These results demonstrate that RSV infection associates with a distinct microRNA fingerprint and suggest that RSV induces inflammatory responses in infants.

Respiratory Syncytial Virus Nonstructural Proteins Upregulate SOCS1 and SOCS3 in the Different Manner from Endogenous IFN Signaling.

Respiratory syncytial virus (RSV) infection upregulates genes of the suppressor of cytokine signaling (SOCS) family, which utilize a feedback loop to inhibit type I interferon dependent antiviral signaling pathway. Here, we reconstituted RSV nonstructural (NS) protein expression plasmids (pNS1, pNS2, and pNS1/2) and tested whether NS1 or NS2 would trigger SOCS1 and SOCS3 protein expression. These NS proteins inhibited interferon- (IFN-) α signaling through a mechanism involving the induction of SOCS1 and SOCS3, which appeared to be different from autocrine IFN dependent. NS1 induced both SOCS1 and SOCS3 upregulation, while NS2 only induced SOCS1 expression. The induced expression of SOCS1 and SOCS3 preceded endogenous IFN-signaling activation and inhibited the IFN-inducible antiviral response as well as chemokine induction. Treatments with INF-α and NS proteins both induced SOCS1 expression; however, they had opposing effects on IFN-α-dependent antiviral gene expression. Our results indicate that NS1 and NS2, which induce the expression of SOCS1 or SOCS3, might represent an independent pathway of stimulating endogenous IFN signaling.

Respiratory syncytial virus nonstructural proteins 1 and 2 are crucial pathogenic factors that modulate interferon signaling and Treg cell distribution in mice.

Respiratory syncytial virus (RSV) nonstructural (NS) proteins 1 and 2 have multiple functions in suppressing the innate immune response and modulating T helper cell subset differentiation. However, little is known about the roles of NS proteins as independent virulence factors. We investigated the effects of recombinant NS1- and NS2-expressing plasmids on the pathogenesis of murine respiratory tissues and splenetic Foxp3+ regulatory T (Treg) cell distribution. Both NS proteins caused weight loss in mice, and NS2 transfection resulted in a persistent weight loss. NS1 dramatically suppressed the induction of interferon beta and interferon-induced GTP-binding protein Mx1. NS1 and NS2 demonstrated different effects in regulating Treg cell differentiation; NS2 increased the proportion of Tregs, whereas NS1 suppressed it. Inhibiting either NS1 or NS2 alleviated the pathology of lung tissues. Thus, NS1 and NS2 are independent pathogenic factors and could be targets for therapeutic strategies in treating RSV infection.