Viral defense at mucosal sites depends on interferons (IFN) and IFN stimulated genes (ISGs), either of which may be constitutively expressed to maintain an "antiviral state (AVS). However, the mechanisms that govern AVS is poorly defined. Using a respiratory epithelial cell line deficient in IRF1, we demonstrate higher susceptibility infection with vesicular stomatitis virus (VSV) influenza. IRF1-mediated restriction VSV IFN-independent, as IRF1 regulates constitutive expression ~250 genes,...

In a genome-wide small interfering RNA (siRNA) screen, we recently identified the interferon (IFN)-inducible protein 35 (IFI35; also known as IFP35) factor required for vesicular stomatitis virus (VSV) infection. Studies reported here were conducted to further understand role and requirement of IFI35 in VSV Consistent with siRNA screening data, found that depletion led reduced replication at level viral gene expression. Although no direct interaction machinery was observed, negatively...

Bunyaviruses are an emerging group of medically important viruses, many which transmitted from insects to mammals. To identify host factors that impact infection, we performed a genome-wide RNAi screen in Drosophila and identified 131 genes impacted infection the mosquito-transmitted bunyavirus Rift Valley fever virus (RVFV). Dcp2, catalytic component mRNA decapping machinery, two activators, DDX6 LSM7, were antiviral against disparate bunyaviruses both insect cells adult flies. 5′ cap their...

Negative-strand (NS) RNA viruses comprise many pathogens that cause serious diseases in humans and animals. Despite their clinical importance, little is known about the host factors required for infection. Using vesicular stomatitis virus (VSV), a prototypic NS family Rhabdoviridae , we conducted human genome-wide siRNA screen identified 72 genes viral Many of these were also infection by two other viruses, lymphocytic choriomeningitis Arenaviridae parainfluenza type 3 Paramyxoviridae...

Alphaviruses are a large class of insect-borne human pathogens and little is known about the host-factor requirements for infection. To identify such factors, we performed genome-wide RNAi screen using model Drosophila cells validated 94 genes that impacted infection Sindbis virus (SINV), prototypical alphavirus. We identified conserved role SEC61A valosin-containing protein (VCP) in facilitating SINV entry insects mammals. VCP selectively regulate trafficking receptor NRAMP2, loss or...

ABSTRACT Previous studies from our laboratory revealed that cellular poly(C) binding protein 2 (PCBP2) downregulates vesicular stomatitis virus (VSV) gene expression. We show here VSV infection induces the formation of granular structures in cytoplasm containing RNA-binding proteins, including PCBP2, T-cell-restricted intracellular antigen 1 (TIA1), and TIA1-related (TIAR). Depletion TIA1 via small interfering RNAs (siRNAs), but not depletion TIAR, results enhanced growth The VSV-induced...

Significance Many viruses, including those of global concern, are dependent on internalization for their entry. We found that ribonuclease kappa (RNASEK) is required infection every virus we tested enters cells through an acid-dependent pathway, dengue, West Nile, Sindbis, Rift Valley Fever, and influenza viruses. Mechanistically, RNASEK has no effect binding to but, rather, uptake. was diverse viruses clathrin-mediated endocytosis entry, but dispensable general endocytic Therefore, appears...

Airway epithelium is both the primary target of and first defense against respiratory syncytial virus (RSV). Whether RSV replicates spreads to adjacent epithelial cells depends on quality their innate immune responses. A549 BEAS-2B are alveolar bronchial cell lines, respectively, that often used study infection. We show permissive infection express genes characteristic a proinflammatory response. In contrast, restrict an antiviral response associated with expression type I III interferons....

Trilogy of Fallot is a rare congenital heart disease consisting pulmonary stenosis, right-to-left interatrial shunt, and right ventricular hypertrophy. It can lead to complications such as thrombus formation result chronic hypoxia leading erythrocytosis hyperviscosity, paradoxical embolisms due the shunt. This report illustrates case young man who presented with cyanosis failure history recurrent episodes transient ischemic attacks. He was found have large atrial thrombus. showed significant...

Abstract Background Peripheral artery disease is commonly managed with percutaneous balloon angioplasty, now the standard for replacing open surgical methods. Although generally effective, this procedure can lead to complications, including rare but potentially fatal vessel perforation. Prompt identification and intervention are crucial avoid severe outcomes. This case report presents a instance of iliac perforation during successfully covered stent. Case summary A 58-year-old male poorly...

A recombinant vesicular stomatitis virus (VSV-PeGFP-M-MmRFP) encoding enhanced green fluorescent protein fused in frame with P (PeGFP) place of and a fusion matrix (monomeric red at the carboxy terminus M [MmRFP]) G-L gene junction, addition to wild-type (wt) its normal location, was recovered, but MmRFP not incorporated into virions. Subsequently, we generated viruses (VSV-PeGFP-DeltaM-Mtc VSV-DeltaM-Mtc) carboxy-terminal tetracysteine tag (Mtc) protein. These Mtc levels similar wt VSV,...

Significance Rift Valley fever virus (RVFV), a mosquito-transmitted bunyavirus, blocks the two common methods of antiviral translational shutdown, PKR and type I interferon. However, it has previously been shown that RVFV infection halts protein production in infected human cells. Here, we demonstrate is restricted by unknown mechanism wherein 5′-terminal oligopyrimidine (5′-TOP) mRNAs encoding core machinery are selectively degraded RNA decapping enzyme NUDT16 during infection, this decay...

Genome uncoating is essential for replication of most viruses. For poxviruses, the process divided into two stages: removal envelope, allowing early gene expression, and breaching core wall, DNA release, replication, late expression. Subsequent studies showed that host proteasome viral D5 protein, which has an role in are required vaccinia virus (VACV) genome uncoating. In a search additional VACV proteins, we noted report described defect expression when encoding 68-kDa ankyrin repeat/F-box...

Significance The innate immune system is a highly conserved mode of defense that induces gene expression programs to restrict microbial infections. However, much remains unknown about how the target genes are poised for their rapid induction. Using Drosophila model, we demonstrate Nup98 plays an essential antiviral role in insects against human insect-borne viruses. Although known its nuclear-cytoplasmic transport, our data suggest this function not at nuclear pore, rather promoters...

ABSTRACT Immunoprecipitation and subsequent mass spectrometry analysis of the cellular proteins from cells expressing vesicular stomatitis virus (VSV) P protein identified poly(C) binding 2 (PCBP2) as one protein-interacting proteins. To investigate role PCBP2 in viral life cycle, we examined effects depletion or overexpression this on VSV growth. Small interfering RNA-mediated silencing promoted replication. Conversely, transfected suppressed Further studies revealed that negatively...

Significance Viruses are important causes of human disease and provide tools for understanding host immune defense mechanisms. Poxviruses good models probing the system because many replicate well in cells, some cause severe disease, nearly half 200 viral genes devoted to interactions. The virus/host equilibrium can be perturbed by mutating a gene restored suppressing opposing genes. To find relevant one such poxvirus mutation, we used high-throughput genome-wide RNAi screen monitored virus...

Abstract Background PVs (PV) are small, non-enveloped, double-stranded DNA viruses that have been identified as the primary etiological agent for cervical cancer and their potential malignant transformation in mucosal tissue has a large impact on public health. The PV family Papillomaviridae is organized into multiple genus based sequential parsimony, host range, tropism, histology. We focused this analysis late gene products, major (L1) minor (L2) capsid proteins from Alpha-papillomavirus....

ABSTRACT Upon infection, pathogen recognition leads to a rapidly activated gene expression program that induces antimicrobial effectors clear the invader. We recently found Nup98 regulates of subset antiviral genes restrict disparate RNA virus infections in Drosophila by promoting polymerase occupancy at promoters these genes. How specifically targets loci was unclear; however, it is known participates with transcription factors regulate developmental-gene activation. reasoned additional may...

ABSTRACT The nucleocapsid protein (N) of vesicular stomatitis virus and other rhabdoviruses plays a central role in the assembly template functions viral N-RNA complex. crystal structure complex suggests that region N interacts with RNA. Sequence alignment rhabdovirus proteins revealed several highly conserved regions, one which spanned residues 282 to 291 (GLSSKSPYSS) molecule. Alanine-scanning mutagenesis this suggested replacement tyrosine residue at position 289 (Y289) alanine resulted...