Human RSV causes an annual epidemic of respiratory tract illness in infants and in elderly. Mechanisms by which RSV antagonizes IFN-mediated antiviral responses include inhibition of type I IFN mRNA transcription and blocking signal transduction of JAK/STAT family members. The suppressor of cytokines signaling (SOCS) gene family utilizes a feedback loop to inhibit cytokine responses and block the activation of the JAK/STAT signaling pathway. To evaluate the potential of SOCS molecules to subvert the innate immune response to RSV infection, eight SOCS family genes were examined. RSV infection up-regulated SOCS1, SOCS3, and CIS mRNA expression in HEp-2 cells. Suppression of SOCS1, SOCS3 and CIS by short interfering ribonucleic acid (siRNA) inhibited viral replication. Furthermore, inhibition of SOCS1, SOCS3, or CIS activated type I IFN signaling by inducing STAT1/2 phosphorylation. These results suggest that RSV infection escapes the innate antiviral response by inducing SOCS1, SOCS3 or CIS expression in epithelial cells.

To evaluate whether KL-6 concentration is a useful biomarker of the severity of respiratory syncytial virus (RSV) bronchiolitis, we determined KL-6 concentrations in patients with RSV bronchiolitis with or without chronic heart disease (CHD). We enrolled 52 patients who had been diagnosed with RSV bronchiolitis and required admission to the hospital at the Department of Pediatrics of Fukushima Medical University School of Medicine from 2004 to 2005. These patients were divided into two groups: Group 1 consisted of patients without any underlying disease, and Group 2 consisted of patients with CHD. These patients were assigned to three categories. Stage A consisted of patients without oxygen dosage, stage B of patients who required oxygen dosage, and stage C of patients required artificial respiration. We evaluated baseline characteristics, clinical features, and serum KL-6 concentration in Group 1, Group 2, and a control group (healthy infants without infection). Mean serum KL-6 concentrations in patients with RSV bronchiolitis were higher than those in the control group (471.8 +/- 236.9 and 127.1 +/- 69.1 U/ml, respectively). Mean serum KL-6 concentration was higher in Group 2 than in Group 1 (692.8 +/- 313.1 and 390.4 +/- 132.7 U/ml, respectively). Mean serum KL-6 concentrations were higher in stage C than in stages A and B, and mean serum KL-6 concentrations were higher in stage B than in stage A. These findings suggest that serum KL-6 is associated with the severity of RSV bronchiolitis and that it may be a useful biomarker for the severity of RSV bronchiolitis.

Subacute sclerosing panencephalitis (SSPE) is a persistent, progressive, and fatal degenerative disease resulting from persistent measles virus (MV) infection of the central nervous system. Most drugs used to treat SSPE have been reported to have limited effects. Therefore, novel therapeutic strategies are urgently required. The SSPE virus, a variant MV strain, differs virologically from wild-type MV strain. One characteristic of the SSPE virus is its defective production of cell-free virus, which leaves cell-to-cell infection as the major mechanism of viral dissemination. The fusion protein plays an essential role in this cell-to-cell spread. It contains two critical heptad repeat regions that form a six-helix bundle in the trimer similar to most viral fusion proteins. In the case of human immunodeficiency virus type-1 (HIV-1), a synthetic peptide derived from the heptad repeat region of the fusion protein enfuvirtide inhibits viral replication and is clinically approved as an anti-HIV-1 agent. The heptad repeat regions of HIV-1 are structurally and functionally similar to those of the MV fusion protein. We therefore designed novel peptides derived from the fusion protein heptad repeat region of the MV and examined their effects on the measles and SSPE virus replication in vitro and in vivo. Some of these synthetic novel peptides demonstrated high antiviral activity against both the measles (Edmonston strain) and SSPE (Yamagata-1 strain) viruses at nanomolar concentrations with no cytotoxicity in vitro. In particular, intracranial administration of one of the synthetic peptides increased the survival rate from 0% to 67% in an SSPE virus-infected nude mouse model.

Investigators conducted a retrospective epidemiological study of subacute sclerosing panencephalitis, a fatal disease caused by measles infection, over the past few years in Japan. Data on 118 cases obtained from a questionnaire sent to attending physicians were analyzed. The annual incidence of subacute sclerosing panencephalitis was approximately 0.03 cases per million from 2001 to 2005. Children infected with measles at a young age (<12 months) showed a high incidence of subacute sclerosing panencephalitis, and those infected before 6 months of age showed earlier onset. Because a positive correlation was found between the prevalence of measles and the onset of subacute sclerosing panencephalitis, particularly among children infected at an early age, it is vital to eradicate measles infection by vaccination.

Myeloid-related protein (MRP) 8/14 complex is a marker of monocyte and neutrophil activation. We evaluated whether serum MRP8/14 complex is associated with clinical manifestations and pathological findings of Henoch-Schönlein purpura nephritis (HSPN). Patients were divided into two groups based on serum MRP8/14 complex levels at renal biopsy. Group 1 consisted of 18 HSPN patients with less than median (670 ng/ml) MRP8/14 complex levels, and Group 2 of 12 HSPN patients with greater than median levels. Clinical manifestations, laboratory findings and serum E-selectin levels, as a marker of vascular endothelial cell dysfunction, as well as histological and immunohistochemical findings were investigated for both groups. We also measured MRP8/14 complex levels in disease control and healthy control children. Urinary protein excretions, serum MRP8/14 complex levels, and serum E-selectin levels were all higher in Group 2 than in Group 1 patients. Serum MRP8/14 complex levels were higher in HSPN patients than in controls. Serum MRP8/14 complex levels were strongly associated with serum E-selectin levels. Pathological findings revealed that the proportions of patients with ISKDC grades III, IV and V in Group 2 were higher than in Group 1. Our findings suggest that serum MRP8/14 complex levels might be associated with the severity of renal injury and endothelial cell dysfunction in HSPN patients.