Measles virus C protein suppresses gamma-activated factor formation and virus-induced cell growth arrest

AbstractMeasles virus (MeV) produces two accessory proteins, V and C, from the P gene. These accessory proteins have been reported to contribute to efficient virus proliferation through the modulation of host cell events. Our previous paper described that Vero cell-adapted strains of MeV led host cells to growth arrest through the upregulation of interferon regulatory factor 1 (IRF-1), and wild strains did not. In the present study, we found that C protein expression levels varied among MeV strains in infected SiHa cells. C protein levels were inversely correlated with IRF-1 expression levels and with cell growth arrest. Forced expression of C protein released cells from growth arrest. C-deficient recombinant virus efficiently upregulated IRF-1 and caused growth arrest more efficiently than the wild-type virus. C protein preferentially bound to phosphorylated STAT1 and suppressed STAT1 dimer formation. We conclude that MeV C protein suppresses IFN-γ signaling pathway via inhibition of phosphorylated STAT1 dimerization

The Battle between Virus and Host: Modulation of Toll-Like Receptor Signaling Pathways by Virus Infection

In order to establish an infection, viruses need to either suppress or escape from host immune defense systems. Recent immunological research has focused on innate immunity as the first line of host defense, especially pattern recognition molecules such as Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and NOD-like receptors (NLRs). Various microbial components are recognized by their vague and common molecular shapes so-called, pathogen-associated molecular patterns (PAMPs). PAMPs induce inflammatory reactions mediated by the activation of the transcription factor, NF-κB, and by interferons, which lead to an antiviral immune response. Viruses have the capacity to suppress or escape from this pattern recognition molecule-mediated antimicrobial response in various ways. In this paper, we review the various strategies used by viruses to modulate the pattern recognition molecule-mediated innate immune response

Clarithromycin Suppresses Human Respiratory Syncytial Virus Infection-Induced Streptococcus pneumoniae Adhesion and Cytokine Production in a Pulmonary Epithelial Cell Line

Human respiratory syncytial virus (RSV) sometimes causes acute and severe lower respiratory tract illness in infants and young children. RSV strongly upregulates proinflammatory cytokines and the platelet-activating factor (PAF) receptor, which is a receptor for Streptococcus pneumoniae, in the pulmonary epithelial cell line A549. Clarithromycin (CAM), which is an antimicrobial agent and is also known as an immunomodulator, significantly suppressed RSV-induced production of interleukin-6, interleukin-8, and regulated on activation, normal T-cell expressed and secreted (RANTES). CAM also suppressed RSV-induced PAF receptor expression and adhesion of fluorescein-labeled S. pneumoniae cells to A549 cells. The RSV-induced S. pneumoniae adhesion was thought to be mediated by the host cell's PAF receptor. CAM, which exhibits antimicrobial and immunomodulatory activities, was found in this study to suppress the RSV-induced adhesion of respiratory disease-causing bacteria, S. pneumoniae, to host cells. Thus, CAM might suppress immunological disorders and prevent secondary bacterial infections during RSV infection

Contrast-enhanced Computed Tomography Screening Is Effective for Detecting Venous Thromboembolism not Prevented by Prophylaxis after Total Knee Arthroplasty

Venous thromboembolism (VTE) is a potential complication occurring after total knee arthroplasty (TKA). We investigated the incidence of VTE after TKA using contrast-enhanced computed tomography (CT), and assessed the efficacy of VTE prophylaxis (fondaparinux and enoxaparin). At our hospital, 189 patients (225 knees) underwent TKA between April 2007 and October 2011. The 225 knees were divided into a control group with no VTE prophylaxis (31 cases), a fondaparinux group (107 cases), and an enoxaparin group (87 cases). Contrast-enhanced CT screening for VTE was performed in all cases on day 5 or 6 after TKA. D-dimer levels were measured on day 5 after TKA, and were significantly lower in the fondaparinux (9.8±3.8) and enoxaparin groups (9.4±4.9) than in the control group (15.6±9.8) (p＜0.001). However, no statistically significant difference in the incidence of VTE was observed among the groups (control, 61.3%;fondaparinux, 49.5%;enoxaparin, 50.6%). Prophylaxis was not effective for the prevention of VTE as detected by contrast-enhanced CT after TKA. CT should be performed after TKA, even when VTE prophylaxis is used

スイカン ヒユゴウ ニ ガッペイ シタ スイカンナイ ニュウトウ シュヨウ ノ イチセツジョレイ

We report a case of partial pancreas divisum with Intraductal Papillary Mucinous Tumor (IPMT) that was performed pancreatic segmentectomy. A 68-year-old woman was admitted to our hospital because she was pointed out a cystic tumor of the pancreatic body by near doctor. Abdominal ultrasonography and endoscopic retrograde pancreaticography showed a partial pancreas divisum and cystic tumor with small elevated lesion. Based on these various examinations a diagnosis partial pancreas divisum with IPMT was determined. Then we performed a minimal invasive operation, and underwent pancreatic segmentectomy. After the operation there were no major complications and she discharged on 34th post operative days. In a review of the Japanese literature, only three such cases including our case have been reported so far

Suppression of Interferon-induced Oligo-2\u27, 5\u27-adenylate Synthetase Induction in Human Hepatoma Cell Line, Li-7

Induction of oligo-2\u27, 5\u27-adenylate synthetase (2-5AS) activity by interferon (IFN) was investigated in a human hepatoma cell line, Li-7 cells. Little induction of 2-5AS activity by IFN was demonstrated in Li-7 cells in comparison with other types of cell lines including Ramos, NC-37, FL, Co-3. Furthermore, failure to induce 2-5AS was much clearer in old-cultured cells. Cell growth inhibition by IFN was demonstrated in only high titers of IFN (>10? IU/ml), in which the enzyme had one hundred fold higher activity than that of untreated cells. Poor induction of 2-5AS was in part the result of some inhibitor presented in cellular extracts of Li-7 cells and the decreased level of 2-5AS mRNA transcription

Elucidation of the mechanism of subunit exchange in αB crystallin oligomers

AlphaB crystallin (αB-crystallin) is a key protein for maintaining the long-term transparency of the eye lens. In the eye lens, αB-crystallin is a “dynamical” oligomer regulated by subunit exchange between the oligomers. To elucidate the unsettled mechanism of subunit exchange in αB-crystallin oligomers, the study was carried out at two different protein concentrations, 28.5 mg/mL (dense sample) and 0.45 mg/mL (dilute sample), through inverse contrast matching small-angle neutron scattering. Interestingly, the exchange rate of the dense sample was the same as that of the dilute sample. From analytical ultracentrifuge measurements, the coexistence of small molecular weight components and oligomers was detected, regardless of the protein concentration. The model proposed that subunit exchange could proceed through the assistance of monomers and other small oligomers; the key mechanism is attaching/detaching monomers and other small oligomers to/from oligomers. Moreover, this model successfully reproduced the experimental results for both dense and dilute solutions. It is concluded that the monomer and other small oligomers attaching/detaching mainly regulates the subunit exchange in αB-crystallin oligomer

Correlation between Oligo-2\u27, 5\u27-adenylate Synthetase and Expression of Human T-Lymphotropic Virus Type-I Specific gag Protein

The effect of human interferon-α (IFN-α) on the production of virus specific gag protein was investigated in four human T cell lines persistently in-fected with human T-lymphotropic virus type-I (HTLV-I). These four cell lines (MT-2, SMT-1, HUT 102, and OKM-2) differed in sensitivity to the func-tions (antivirus activity, antiproliferative activity, and oligo-2\u27, 5\u27-adenylate synthetase induction) of IFN. The expression of HTLV-I gag-protein, p 53, p 33, p 28, p 24, and p 19, was found in each IFN-α or non-treated cell lines by Western blotting analysis. However, production of p 33, p 28 and p 24 was different among these cell lines. Protein bands of p 53, p 28, p 24, and p 19 were detected in MT-2 cell lines, and p 33 was found in SMT-1 and OKM-2 cell lines instead of p 28. Those of p 28 and p 24 were undetectable in HUT 102 cell line. Furthermore, the expression of these virus antigens was hardly affected by exogenously added IFN-α in spite of the induction of oligo-2\u27, 5\u27-adenylate synthetase (2-5AS) activity

RSV replication is attenuated by counteracting expression of the suppressor of cytokine signaling (SOCS) molecules

AbstractHuman 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