ABSTRACT Dengue virus (DENV) replication is inhibited by the prior addition of type I interferon or RIG-I agonists that elicit RIG-I/MAVS/TBK1/IRF3-dependent protective responses. DENV infection primary human endothelial cells (ECs) results in a rapid increase viral titer, which suggests inhibits replication-restrictive RIG-I/interferon beta (IFN-β) induction pathways within ECs. Our findings demonstrate serotype 4 (DENV4) nonstructural (NS) proteins NS2A and NS4B RIG-I-, MDA5-, MAVS-,...

The signal transducer and activator of transcription-3 (STAT3) induces transcription genes that control differentiation, inflammation, proliferation, tumor cell invasion. Cytokines such as interleukin-6 interferon stimulate the specific tyrosine phosphorylation STAT3, which confers its ability to bind consensus DNA targets. In addition, unphosphorylated STAT3 has been demonstrated induce gene expression. must gain entrance nucleus impact transcription, however access is a tightly regulated...

Rhabdoid tumors (RT) are aggressive pediatric malignancies with poor prognosis. INI1/hSNF5 is a component of the chromatin remodeling SWI/SNF complex and tumor suppressor deleted in RT. Previous microarray studies indicated that reintroduction into RT cells leads to repression high degree mitotic genes including Aurora Kinase A (Aurora A, STK6). Here, we found INI1/SNF5 represses transcription cell-type-specific manner. INI1-mediated was observed normal but not non-RT cell lines. Chromatin...

Hantaviruses successfully replicate in primary human endothelial cells by restricting the early induction of beta interferon (IFN-β) and interferon-stimulated genes (ISGs). Gn proteins from NY-1V, ANDV, TULV, but not PHV, harbor elements their 142-residue cytoplasmic tails (GnTs) that inhibit RIG-I/MAVS/TBK1-TRAF3-directed IFN-β induction. Here, we define GnT interactions residues required to TRAF3-TBK1-directed IRF3 phosphorylation. We observed GnTs bind TRAF3 via within TRAF-N domain...

ABSTRACT Andes virus (ANDV) is the only hantavirus known to spread from person and shown cause highly lethal pulmonary syndrome (HPS) in patients Syrian hamsters. Hantaviruses replicate human endothelial cells accomplish this by restricting early induction of beta interferon (IFN-β)- IFN-stimulated genes (ISGs). Our studies reveal that ANDV nucleocapsid (N) protein uniquely inhibits IFN signaling responses directed cytoplasmic double-stranded RNA (dsRNA) sensors RIG-I MDA5. In contrast, N...

ABSTRACT Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants and children represents an important global health burden for elderly immunocompromised. Despite decades research efforts, no licensed vaccine RSV available. We have developed virus-like particle (VLP)-based vaccines assembled with human metapneumovirus (hMPV) matrix protein (M) as structural scaffold fusion glycoprotein (F) either postfusion or prefusion conformation its prime surface...

A dengue vaccine capable of rapidly eliciting a robust and balanced immunity against the four virus serotypes after only few immunizations is greatly needed. We describe new strategy to develop vaccines based on assembly virus-like particles (VLPs) utilizing structural proteins CprME together with modified complex NS2B/NS3 protease, which enhances particle formation yield. These VLPs are produced in mammalian cells resemble native as demonstrated by negative staining immunogold labelling...

Available evidence suggests that the antischistosomal drug oxamniquine is converted to a reactive ester by schistosome enzyme missing in drug-resistant parasites. This study presents data supporting idea active sulfate and activating sulfotransferase. Evidence comes from fact parasite extract loses its capability upon dialysis, implying requirement of some dialyzable cofactor. The addition donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) restored activity dialyzate, strong indication...

Abstract Purpose: Rhabdoid tumors are rare but aggressive pediatric malignancies characterized by biallelic loss of INI1/hSNF5. Reintroduction INI1 causes cell arrest and senescence in rhabdoid cells. Our purpose was to identify INI1-downstream genes determine their functional therapeutic significance for tumors. Experimental Design: downstream targets cells were identified using a cDNA microarray analysis the expression selected confirmed quantitative reverse transcription-PCR, Western...

Abstract Purpose: Rhabdoid tumors are aggressive and incurable pediatric malignancies. INI1/hSNF5, a tumor suppressor biallelically deleted/inactivated in rhabdoid tumors, directly represses cyclin D1. cells exquisitely dependent on D1 for genesis survival, suggesting that targeting the cyclin/cyclin-dependent kinase (cdk) axis may be an effective therapeutic strategy these tumors. Because cdk inhibitors have not been used preclinical or clinical testing we investigated effect of...

Rhabdoid tumors (RTs) are rare, highly aggressive pediatric malignancies with poor prognosis and no standard or effective treatment strategies. RTs characterized by biallelic inactivation of the INI1 tumor suppressor gene. directly represses CCND1 activates cyclin-dependent kinase (cdk) inhibitors p16 Ink4a p21 CIP . exquisitely dependent on cyclin D1 for genesis survival. To facilitate translation unique therapeutic strategies, we have used genetically engineered, Ini1 +/− mice testing. We...

Rhabdoid Tumors (RTs) are highly aggressive pediatric malignancies with poor prognosis. There currently no standard or effective treatments for RTs in part because not designed to specifically target these tumors. Our previous studies indicated that targeting the cyclin/cdk pathway is a novel therapeutic strategy and pan-cdk inhibitor, flavopiridol, inhibits RT growth. Since toxicities narrow window of activity associated flavopiridol may limit its clinical use, we tested effect combining...

Powassan virus (POWV) is a tick-borne flavivirus circulating in North America and the Russian Far East that can cause severe neuroinvasive diseases, including encephalitis, meningitis, meningoencephalitis. The reported case fatality about 10%, approximately 50% of survivors from neuroinfection exhibit long-lasting or permanent neurological sequelae. Currently, treatment POWV infection supportive, no FDA-approved vaccines specific therapeutics are available. A novel vaccine candidate was...

The inflammatory cytokine IL-6 is known to play a causal role in the promotion of cancer, although underlying mechanisms remain be completely understood. Interplay between endogenous and environmental cues determines fate cancer development. Eμ- myc transgenic mouse expresses elevated levels c-Myc B cell lineage develops lymphomas with associated mutations p53 or other genes linked apoptosis. We generated mice that either lacked gene, STAT3 gene specifically cells determine IL-6/JAK/STAT3...

Supplementary Figures 1-3 from <i>Aurora A</i> Is a Repressed Effector Target of the Chromatin Remodeling Protein INI1/hSNF5 Required for Rhabdoid Tumor Cell Survival