Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene

Nature ◽  
1993 ◽  
Vol 361 (6414) ◽  
pp. 739-742 ◽  
Author(s):  
Beth Levine ◽  
Qi Huang ◽  
John T. Isaacs ◽  
John C. Reed ◽  
Diane E. Griffin ◽  
...  
Keyword(s):  
Cellular Oncogene ◽  
Alphavirus Infection

First confirmation of salmonid alphavirus infection in Arctic char Salvelinus alpinus and in Austria

2018 ◽  
Vol 130 (1) ◽  
pp. 71-76
Author(s):  
E Lewisch ◽  
T Frank ◽  
H Soliman ◽  
O Schachner ◽  
A Friedl ◽  
...  
Keyword(s):  
Salvelinus Alpinus ◽  
Arctic Char ◽  
Alphavirus Infection

Near-germline human monoclonal antibodies neutralize and protect against multiple arthritogenic alphaviruses

2021 ◽  
Vol 118 (37) ◽  
pp. e2100104118
Author(s):  
Ryan J. Malonis ◽  
James T. Earnest ◽  
Arthur S. Kim ◽  
Matthew Angeliadis ◽  
Frederick W. Holtsberg ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Human Mabs ◽  
Isolation And Characterization ◽  
Neutralizing Capacity ◽  
Rheumatological Disease ◽  
Mayaro Virus ◽  
Alphavirus Infection ◽  
Globally Distributed

Arthritogenic alphaviruses are globally distributed, mosquito-transmitted viruses that cause rheumatological disease in humans and include Chikungunya virus (CHIKV), Mayaro virus (MAYV), and others. Although serological evidence suggests that some antibody-mediated heterologous immunity may be afforded by alphavirus infection, the extent to which broadly neutralizing antibodies that protect against multiple arthritogenic alphaviruses are elicited during natural infection remains unknown. Here, we describe the isolation and characterization of MAYV-reactive alphavirus monoclonal antibodies (mAbs) from a CHIKV-convalescent donor. We characterized 33 human mAbs that cross-reacted with CHIKV and MAYV and engaged multiple epitopes on the E1 and E2 glycoproteins. We identified five mAbs that target distinct regions of the B domain of E2 and potently neutralize multiple alphaviruses with differential breadth of inhibition. These broadly neutralizing mAbs (bNAbs) contain few somatic mutations and inferred germline–revertants retained neutralizing capacity. Two bNAbs, DC2.M16 and DC2.M357, protected against both CHIKV- and MAYV-induced musculoskeletal disease in mice. These findings enhance our understanding of the cross-reactive and cross-protective antibody response to human alphavirus infections.

scholarly journals Subgenomic Reporter RNA System for Detection of Alphavirus Infection in Mosquitoes

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e84930 ◽  
Author(s):  
J. Jordan Steel ◽  
Alexander W. E. Franz ◽  
Irma Sanchez-Vargas ◽  
Ken E. Olson ◽  
Brian J. Geiss
Keyword(s):  
Alphavirus Infection

scholarly journals The Interferon-Stimulated Gene IFITM3 Restricts Infection and Pathogenesis of Arthritogenic and Encephalitic Alphaviruses

2016 ◽  
Vol 90 (19) ◽  
pp. 8780-8794 ◽  
Author(s):  
Subhajit Poddar ◽  
Jennifer L. Hyde ◽  
Matthew J. Gorman ◽  
Michael Farzan ◽  
Michael S. Diamond
Keyword(s):  
Viral Infections ◽  
Transmembrane Protein ◽  
Flow Cytometric Analysis ◽  
Antiviral Effect ◽  
Host Cells ◽  
Type I ◽  
Targeted Gene Deletion ◽  
Multiple Organs ◽  
Viral Burden ◽  
Alphavirus Infection

ABSTRACTHost cells respond to viral infections by producing type I interferon (IFN), which induces the expression of hundreds of interferon-stimulated genes (ISGs). Although ISGs mediate a protective state against many pathogens, the antiviral functions of the majority of these genes have not been identified. IFITM3 is a small transmembrane ISG that restricts a broad range of viruses, including orthomyxoviruses, flaviviruses, filoviruses, and coronaviruses. Here, we show that alphavirus infection is increased inIfitm3−/−andIfitmlocus deletion (Ifitm-del) fibroblasts and, reciprocally, reduced in fibroblasts transcomplemented with Ifitm3. Mechanistic studies showed that Ifitm3 did not affect viral binding or entry but inhibited pH-dependent fusion. In a murine model of chikungunya virus arthritis,Ifitm3−/−mice sustained greater joint swelling in the ipsilateral ankle at days 3 and 7 postinfection, and this correlated with higher levels of proinflammatory cytokines and viral burden. Flow cytometric analysis suggested thatIfitm3−/−macrophages from the spleen were infected at greater levels than observed in wild-type (WT) mice, results that were supported by experiments withIfitm3−/−bone marrow-derived macrophages.Ifitm3−/−mice also were more susceptible than WT mice to lethal alphavirus infection with Venezuelan equine encephalitis virus, and this was associated with greater viral burden in multiple organs. Collectively, our data define an antiviral role for Ifitm3 in restricting infection of multiple alphaviruses.IMPORTANCEThe interferon-induced transmembrane protein 3 (IFITM3) inhibits infection of multiple families of viruses in cell culture. Compared to other viruses, much less is known about the antiviral effect of IFITM3 on alphaviruses. In this study, we characterized the antiviral activity of mouse Ifitm3 against arthritogenic and encephalitic alphaviruses using cells and animals with a targeted gene deletion ofIfitm3as well as deficient cells transcomplemented with Ifitm3. Based on extensive virological analysis, we demonstrate greater levels of alphavirus infection and disease pathogenesis when Ifitm3 expression is absent. Our data establish an inhibitory role for Ifitm3 in controlling infection of alphaviruses.

Homology between an endogenous viral LTR and sequences inserted in an activated cellular oncogene

Nature ◽  
1983 ◽  
Vol 302 (5908) ◽  
pp. 547-548 ◽  
Author(s):  
Edward L. Kuff ◽  
Anita Feenstra ◽  
Kira Lueders ◽  
Gideon Rechavi ◽  
David Givol ◽  
...  
Keyword(s):  
Cellular Oncogene

Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour

Nature ◽  
1983 ◽  
Vol 305 (5931) ◽  
pp. 245-248 ◽  
Author(s):  
Manfred Schwab ◽  
Kari Alitalo ◽  
Karl-Heinz Klempnauer ◽  
Harold E. Varmus ◽  
J. Michael Bishop ◽  
...  
Keyword(s):  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Cellular Oncogene ◽  
Neuroblastoma Cell Lines

scholarly journals Macromolecular Synthesis Shutoff Resistance by Myeloid Cells Is Critical to IRF7-Dependent Systemic Interferon Alpha/Beta Induction after Alphavirus Infection

2019 ◽  
Vol 93 (24) ◽  
Author(s):  
Nishank Bhalla ◽  
Christina L. Gardner ◽  
Sierra N. Downs ◽  
Matthew Dunn ◽  
Chengqun Sun ◽  
...  
Keyword(s):  
Host Cell ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Cell Types ◽  
Macromolecular Synthesis ◽  
Transcription Inhibition ◽  
Antiviral Responses ◽  
Alphavirus Infection

ABSTRACT Alphavirus infection of fibroblastic cell types in vitro inhibits host cell translation and transcription, leading to suppression of interferon alpha/beta (IFN-α/β) production. However, the effect of infection upon myeloid cells, which are often the first cells encountered by alphaviruses in vivo, is unclear. Previous studies demonstrated an association of systemic IFN-α/β production with myeloid cell infection efficiency. Murine infection with wild-type Venezuelan equine encephalitis virus (VEEV), a highly myeloid-cell-tropic alphavirus, results in secretion of very high systemic levels of IFN-α/β, suggesting that stress responses in responding cells are active. Here, we infected myeloid cell cultures with VEEV to identify the cellular source of IFN-α/β, the timing and extent of translation and/or transcription inhibition in infected cells, and the transcription factors responsible for IFN-α/β induction. In contrast to fibroblast infection, myeloid cell cultures infected with VEEV secreted IFN-α/β that increased until cell death was observed. VEEV inhibited translation in most cells early after infection (<6 h postinfection [p.i.]), while transcription inhibition occurred later (>6 h p.i.). Furthermore, the interferon regulatory factor 7 (IRF7), but not IRF3, transcription factor was critical for IFN-α/β induction in vitro and in sera of mice. We identified a subset of infected Raw 264.7 myeloid cells that resisted VEEV-induced translation inhibition and secreted IFN-α/β despite virus infection. However, in the absence of IFN receptor signaling, the size of this cell population was diminished. These results indicate that IFN-α/β induction in vivo is IRF7 dependent and arises in part from a subset of myeloid cells that are resistant, in an IFN-α/β-dependent manner, to VEEV-induced macromolecular synthesis inhibition. IMPORTANCE Most previous research exploring the interaction of alphaviruses with host cell antiviral responses has been conducted using fibroblast lineage cell lines. Previous studies have led to the discovery of virus-mediated activities that antagonize host cell antiviral defense pathways, such as host cell translation and transcription inhibition and suppression of STAT1 signaling. However, their relevance and impact upon myeloid lineage cell types, which are key responders during the initial stages of alphavirus infection in vivo, have not been well studied. Here, we demonstrate the different abilities of myeloid cells to resist VEEV infection compared to nonmyeloid cell types and begin to elucidate the mechanisms by which host antiviral responses are upregulated in myeloid cells despite the actions of virus-encoded antagonists.

Developmental Stages and Energy Restriction Affect Cellular Oncogene Expression in Tissues of Female Rats

1992 ◽  
Vol 122 (8) ◽  
pp. 1614-1619 ◽  
Author(s):  
Myunggi Baik ◽  
Chang B. Choi ◽  
Wanda L. Keller ◽  
Chung S. Park
Keyword(s):  
Developmental Stages ◽  
Energy Restriction ◽  
Female Rats ◽  
Cellular Oncogene ◽  
Oncogene Expression

scholarly journals Effects of Palmitoylation of Replicase Protein nsP1 on Alphavirus Infection

2000 ◽  
Vol 74 (15) ◽  
pp. 6725-6733 ◽  
Author(s):  
Tero Ahola ◽  
Pekka Kujala ◽  
Minna Tuittila ◽  
Titta Blom ◽  
Pirjo Laakkonen ◽  
...  
Keyword(s):  
Sindbis Virus ◽  
Semliki Forest Virus ◽  
Rna Replication ◽  
Cell Types ◽  
Alkaline Solutions ◽  
Nonstructural Proteins ◽  
Replication Complex ◽  
Replication Sites ◽  
Infected Cells ◽  
Alphavirus Infection

ABSTRACT The membrane-associated alphavirus RNA replication complex contains four virus-encoded subunits, the nonstructural proteins nsP1 to nsP4. Semliki Forest virus (SFV) nsP1 is hydrophobically modified by palmitoylation of cysteines 418 to 420. Here we show that Sindbis virus nsP1 is also palmitoylated on the same site (cysteine 420). When mutations preventing nsP1 palmitoylation were introduced into the genomes of these two alphaviruses, the mutant viruses remained viable and replicated to high titers, although their growth was slightly delayed. The subcellular distribution of palmitoylation-defective nsP1 was altered in the mutant: it no longer localized to filopodial extensions, and a fraction of it was soluble. The ultrastructure of the alphavirus replication sites appeared normal, and the localization of the other nonstructural proteins was unaltered in the mutants. In both wild-type- and mutant-virus-infected cells, SFV nsP3 and nsP4 could be extracted from membranes only by alkaline solutions whereas the nsP2-membrane association was looser. Thus, the membrane binding properties of the alphavirus RNA replication complex were not determined by the palmitoylation of nsP1. The nsP1 palmitoylation-defective alphaviruses produced normal plaques in several cell types, but failed to give rise to plaques in HeLa cells, although they induced normal apoptosis of these cells. The SFV mutant was apathogenic in mice: it caused blood viremia, but no infectious virus was detected in the brain.

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