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Host cells respond to viral infection by the production of type I interferons (IFNs), which induce the expression of antiviral genes. Herpes simplex virus I (HSV-1) encodes many mechanisms that inhibit the type I IFN response, including the ICP27-dependent inhibition of type I IFN signaling. Here we show inhibition of Stat-1 nuclear accumulation in cells that express ICP27. ICP27 expression also induces...
The interferon-β (IFN-β) response is critical for protection against viral myocarditis in several mouse models, and IFN-α or -β treatment is beneficial against human viral myocarditis. The IFN-β response in cardiac myocytes and cardiac fibroblasts forms an integrated network for organ protection; however, the different IFN-α subtypes have not been studied in cardiac cells. We developed a quantitative...
Influenza viruses induce a host shut off mechanism leading to the general inhibition of host gene expression in infected cells. Here, we report that the large subunit of host RNA polymerase II (Pol II) is degraded in infected cells and propose that this degradation is mediated by the viral RNA polymerase that associates with Pol II. We detect increased ubiquitylation of Pol II in infected cells and...
The envelope glycoprotein (GP) of Ebolavirus (EBOV) mediates viral entry into host cells. Through mutagenesis, we and other groups reported that two phenylalanines at positions 88 and 159 of GP are critical for viral entry. However, it remains elusive which steps of viral entry are impaired by F88 or F159 mutations and how. In this study, we further characterized these two phenylalanines through mutagenesis...
A type A avian influenza (AI) virus was isolated from dead or severely ill red-winged tinamous (Rhynchotus rufescens) found in a hunting ground in April 2008 in Argentina. The subtype of A/red-winged tinamou/Argentina/MP1/2008 was determined as H1N1 by sequence analysis. The cleavage site of the viral hemagglutinin corresponded to a low pathogenic influenza virus, although the clinical presentation...
In this study we investigated the effect of HPV16 E6 on the Wnt/β-catenin oncogenic signaling pathway. Luciferase reporter assays indicated that ectopically expressed E6 significantly augmented the Wnt/β-catenin/TCF-dependent signaling response in a dose-dependent manner. This activity was independent of the ability of E6 to target p53 for degradation or bind to the PDZ-containing E6 targets. Epistasis...
The vaccinia virus A43R open reading frame encodes a 168-amino acid protein with a predicted N-terminal signal sequence and a C-terminal transmembrane domain. Although A43R is conserved in all sequenced members of the orthopoxvirus genus, no non-orthopoxvirus homolog or functional motif was recognized. Biochemical and confocal microscopic studies indicated that A43 is expressed at late times following...
The coat protein of satellite panicum mosaic virus (SPCP) is known to effectively protect its cognate RNA from deleterious events, and here, we tested its stabilizing potential for heterologous virus-based gene vectors in planta. In support of this, a Potato virus X (PVX) vector carrying the SPMV capsid protein (PVX-SPCP) gene was stable for at least three serial systemic passages through Nicotiana...
A panel of influenza A viruses encoding mutant NS1 proteins was created in which a number of NS1 functions, including interactions with dsRNA, PI3K, CPSF30 and PKR, were inhibited. Surprisingly, given previous reports that NS1 activates PI3K to prevent apoptosis, the mutant viruses rUd-Y89F and rUd-P164/7A that fail to activate PI3K did not induce any more apoptosis than wild-type virus in MRC-5 and...
Processing of Sesbania mosaic virus (SeMV) polyprotein 2a and 2ab was reanalyzed in the view of the new genome organization of sobemoviruses. Polyprotein 2a when expressed in E. coli, from the new cDNA clone, got cleaved at the earlier identified sites E325-T326, E402-T403 and E498-S499 to release protease, VPg, P10 and P8, respectively. Additionally, a novel cleavage was identified within the protease...
Previous genome-wide screens identified >100 host genes affecting tombusvirus replication using yeast model host. One of those factors was Nsr1p (nucleolin), which is an abundant RNA-binding shuttle protein involved in rRNA maturation and ribosome assembly. We find that overexpression of Nsr1p in yeast or in Nicotiana benthamiana inhibited the accumulation of tombusvirus RNA by ∼10-fold. Regulated...
To explore the role in viral pathogenesis of the region located between the two functional AUG (inter-AUG) in foot-and-mouth disease virus (FMDV), we derived viruses containing transposon (tn) inserts from a mutagenized cDNA infectious clone of FMDV (pA24-WT). Mutant viruses containing an in-frame 57-nt transposon insertion grew at a slower rate and had a smaller plaque size phenotype than the parental...
Infection with a broad diversity of viruses often activates host cell signaling pathways including the mitogen-activated protein kinase pathway. The present study established that dengue virus infection of human macrophages activates Jun NH(2)-terminal kinase (JNK) and the p38 MAPKs pathways. The activation was observed at early times after infection and occurs when either infectious or UV-inactivated...
We previously identified the Tomato leaf curl Java virus-A (ToLCJV-A[ID]) from Southeast Asia as a new member of the emerging group of monopartite begomoviruses that require a betasatellite component for symptom induction. In this study, the role of V2 in viral pathogenesis and posttranscriptional gene silencing (PTGS) was studied. Our results showed V2 of ToLCJV-A[ID] elicits a reaction resembling...
The HPV oncoprotein E7 promotes proteasomal degradation of the tumor suppressor protein Rb. In this study, we analyzed the regulation of E7-induced Rb proteolysis in HPV-containing Caski cervical cancer cells. We show that the Rb proteolysis is cell cycle dependent; in S phase Rb is stable while in post-mitotic early G1 phase cells and in differentiated cells, Rb is unstable. Similarly, the in vivo...
Papillomaviruses are DNA viruses that cause tumours of the skin in humans and animals. The natural host of bovine papillomavirus is cattle, but also equids, resulting in tumours termed sarcoids. Matrix metalloproteinase 1 (MMP-1) expression is up-regulated in sarcoid fibroblasts and tumours. We extended our observation to other MMPs and determined whether MMPs induced invasion of sarcoid fibroblasts...
In 1998, an enterovirus 71 (EV71) epidemic in Taiwan resulted in 78 deaths; however, the molecular basis of EV71 pathogenicity remains poorly understood. Comparison of the deduced amino acid sequences in 3D polymerases of EV71clinical isolates showed the T251V or T251I substitution from 1986 and 1998 outbreaks. An EV71 replicon system showed that introducing an I251T mutation did not affect luciferase...
The role of RNA silencing as an antiviral defence has been well elucidated in plants and invertebrates, but not in filamentous fungi. We have previously determined the complete genome sequence of Magnaporthe oryzae virus 2 (MoV2), a dsRNA virus that infects the rice blast fungus Magnaporthe oryzae. In this study, we detected small interfering RNAs (siRNAs) from both positive- and negative-strand MoV2...
Two size forms of ADAR1 adenosine deaminase are known, one constitutively expressed (p110) and the other interferon (IFN)-induced (p150). To test the role of ADAR1 in viral infection, HeLa cells with ADAR1 stably knocked down and 293 cells overexpressing ADAR1 were utilized. Overexpression of p150 ADAR1 had no significant effect on the yield of vesicular stomatitis virus. Likewise, reduction of p110...
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