Cargando…

IIV-6 Inhibits NF-κB Responses in Drosophila

The host immune response and virus-encoded immune evasion proteins pose constant, mutual selective pressure on each other. Virally encoded immune evasion proteins also indicate which host pathways must be inhibited to allow for viral replication. Here, we show that IIV-6 is capable of inhibiting the...

Descripción completa

Detalles Bibliográficos
Autores principales: West, Cara, Rus, Florentina, Chen, Ying, Kleino, Anni, Gangloff, Monique, Gammon, Don B., Silverman, Neal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563256/
https://www.ncbi.nlm.nih.gov/pubmed/31052481
http://dx.doi.org/10.3390/v11050409
_version_ 1783426508470091776
author West, Cara
Rus, Florentina
Chen, Ying
Kleino, Anni
Gangloff, Monique
Gammon, Don B.
Silverman, Neal
author_facet West, Cara
Rus, Florentina
Chen, Ying
Kleino, Anni
Gangloff, Monique
Gammon, Don B.
Silverman, Neal
author_sort West, Cara
collection PubMed
description The host immune response and virus-encoded immune evasion proteins pose constant, mutual selective pressure on each other. Virally encoded immune evasion proteins also indicate which host pathways must be inhibited to allow for viral replication. Here, we show that IIV-6 is capable of inhibiting the two Drosophila NF-κB signaling pathways, Imd and Toll. Antimicrobial peptide (AMP) gene induction downstream of either pathway is suppressed when cells infected with IIV-6 are also stimulated with Toll or Imd ligands. We find that cleavage of both Imd and Relish, as well as Relish nuclear translocation, three key points in Imd signal transduction, occur in IIV-6 infected cells, indicating that the mechanism of viral inhibition is farther downstream, at the level of Relish promoter binding or transcriptional activation. Additionally, flies co-infected with both IIV-6 and the Gram-negative bacterium, Erwinia carotovora carotovora, succumb to infection more rapidly than flies singly infected with either the virus or the bacterium. These findings demonstrate how pre-existing infections can have a dramatic and negative effect on secondary infections, and establish a Drosophila model to study confection susceptibility.
format Online
Article
Text
id pubmed-6563256
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-65632562019-06-17 IIV-6 Inhibits NF-κB Responses in Drosophila West, Cara Rus, Florentina Chen, Ying Kleino, Anni Gangloff, Monique Gammon, Don B. Silverman, Neal Viruses Article The host immune response and virus-encoded immune evasion proteins pose constant, mutual selective pressure on each other. Virally encoded immune evasion proteins also indicate which host pathways must be inhibited to allow for viral replication. Here, we show that IIV-6 is capable of inhibiting the two Drosophila NF-κB signaling pathways, Imd and Toll. Antimicrobial peptide (AMP) gene induction downstream of either pathway is suppressed when cells infected with IIV-6 are also stimulated with Toll or Imd ligands. We find that cleavage of both Imd and Relish, as well as Relish nuclear translocation, three key points in Imd signal transduction, occur in IIV-6 infected cells, indicating that the mechanism of viral inhibition is farther downstream, at the level of Relish promoter binding or transcriptional activation. Additionally, flies co-infected with both IIV-6 and the Gram-negative bacterium, Erwinia carotovora carotovora, succumb to infection more rapidly than flies singly infected with either the virus or the bacterium. These findings demonstrate how pre-existing infections can have a dramatic and negative effect on secondary infections, and establish a Drosophila model to study confection susceptibility. MDPI 2019-05-01 /pmc/articles/PMC6563256/ /pubmed/31052481 http://dx.doi.org/10.3390/v11050409 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
West, Cara
Rus, Florentina
Chen, Ying
Kleino, Anni
Gangloff, Monique
Gammon, Don B.
Silverman, Neal
IIV-6 Inhibits NF-κB Responses in Drosophila
title IIV-6 Inhibits NF-κB Responses in Drosophila
title_full IIV-6 Inhibits NF-κB Responses in Drosophila
title_fullStr IIV-6 Inhibits NF-κB Responses in Drosophila
title_full_unstemmed IIV-6 Inhibits NF-κB Responses in Drosophila
title_short IIV-6 Inhibits NF-κB Responses in Drosophila
title_sort iiv-6 inhibits nf-κb responses in drosophila
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563256/
https://www.ncbi.nlm.nih.gov/pubmed/31052481
http://dx.doi.org/10.3390/v11050409
work_keys_str_mv AT westcara iiv6inhibitsnfkbresponsesindrosophila
AT rusflorentina iiv6inhibitsnfkbresponsesindrosophila
AT chenying iiv6inhibitsnfkbresponsesindrosophila
AT kleinoanni iiv6inhibitsnfkbresponsesindrosophila
AT gangloffmonique iiv6inhibitsnfkbresponsesindrosophila
AT gammondonb iiv6inhibitsnfkbresponsesindrosophila
AT silvermanneal iiv6inhibitsnfkbresponsesindrosophila