Putative endogenous filovirus VP35-like protein potentially functions as an IFN antagonist but not a polymerase cofactor

Tatsunari Kondoh, Rashid Manzoor, Naganori Nao, Junki Maruyama, Wakako Furuyama, Hiroko Miyamoto, Asako Shigeno, Makoto Kuroda, Keita Matsuno, Daisuke Fujikura, Masahiro Kajihara, Reiko Yoshida, Manabu Igarashi, Ayato Takada

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

It has been proposed that some non-retroviral RNA virus genes are integrated into vertebrate genomes. Endogenous filovirus-like elements (EFLs) have been discovered in some mammalian genomes. However, their potential roles in ebolavirus infection are unclear. A filovirus VP35-like element (mlEFL35) is found in the little brown bat (Myotis lucifugus) genome. Putative mlEFL35-derived protein (mlEFL35p) contains nearly full-length amino acid sequences corresponding to ebolavirus VP35. Ebola virus VP35 has been shown to bind double-stranded RNA, leading to inhibition of type I interferon (IFN) production, and is also known as a viral polymerase cofactor that is essential for viral RNA transcription/replication. In this study, we transiently expressed mlEFL35p in human kidney cells and investigated its biological functions. We first found that mlEFL35p was coimmunoprecipitated with itself and ebolavirus VP35s but not with the viral nucleoprotein. Then the biological functions of mlEFL35p were analyzed by comparing it to ebolavirus VP35s. We found that the expression of mlEFL35p significantly inhibited human IFN-β promoter activity as well as VP35s. By contrast, expression of mlEFL35p did not support viral RNA transcription/replication and indeed slightly decrease the reporter gene expression in a minigenome assay. These results suggest that mlEFL35p potentially acts as an IFN antagonist but not a polymerase cofactor.

Original languageEnglish (US)
Article numbere0186450
JournalPLoS One
Volume12
Issue number10
DOIs
StatePublished - Oct 1 2017
Externally publishedYes

Fingerprint

Filoviridae
Ebolavirus
interferons
Interferons
antagonists
Genes
Proteins
proteins
Viral RNA
Genome
Transcription
genome
transcription (genetics)
RNA
Interferon Type I
nucleoproteins
Nucleoproteins
Double-Stranded RNA
RNA Viruses
double-stranded RNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Putative endogenous filovirus VP35-like protein potentially functions as an IFN antagonist but not a polymerase cofactor. / Kondoh, Tatsunari; Manzoor, Rashid; Nao, Naganori; Maruyama, Junki; Furuyama, Wakako; Miyamoto, Hiroko; Shigeno, Asako; Kuroda, Makoto; Matsuno, Keita; Fujikura, Daisuke; Kajihara, Masahiro; Yoshida, Reiko; Igarashi, Manabu; Takada, Ayato.

In: PLoS One, Vol. 12, No. 10, e0186450, 01.10.2017.

Research output: Contribution to journalArticle

Kondoh, T, Manzoor, R, Nao, N, Maruyama, J, Furuyama, W, Miyamoto, H, Shigeno, A, Kuroda, M, Matsuno, K, Fujikura, D, Kajihara, M, Yoshida, R, Igarashi, M & Takada, A 2017, 'Putative endogenous filovirus VP35-like protein potentially functions as an IFN antagonist but not a polymerase cofactor', PLoS One, vol. 12, no. 10, e0186450. https://doi.org/10.1371/journal.pone.0186450
Kondoh, Tatsunari ; Manzoor, Rashid ; Nao, Naganori ; Maruyama, Junki ; Furuyama, Wakako ; Miyamoto, Hiroko ; Shigeno, Asako ; Kuroda, Makoto ; Matsuno, Keita ; Fujikura, Daisuke ; Kajihara, Masahiro ; Yoshida, Reiko ; Igarashi, Manabu ; Takada, Ayato. / Putative endogenous filovirus VP35-like protein potentially functions as an IFN antagonist but not a polymerase cofactor. In: PLoS One. 2017 ; Vol. 12, No. 10.
@article{abffac24fb924ccfa5aed7fe1f1b254d,
title = "Putative endogenous filovirus VP35-like protein potentially functions as an IFN antagonist but not a polymerase cofactor",
abstract = "It has been proposed that some non-retroviral RNA virus genes are integrated into vertebrate genomes. Endogenous filovirus-like elements (EFLs) have been discovered in some mammalian genomes. However, their potential roles in ebolavirus infection are unclear. A filovirus VP35-like element (mlEFL35) is found in the little brown bat (Myotis lucifugus) genome. Putative mlEFL35-derived protein (mlEFL35p) contains nearly full-length amino acid sequences corresponding to ebolavirus VP35. Ebola virus VP35 has been shown to bind double-stranded RNA, leading to inhibition of type I interferon (IFN) production, and is also known as a viral polymerase cofactor that is essential for viral RNA transcription/replication. In this study, we transiently expressed mlEFL35p in human kidney cells and investigated its biological functions. We first found that mlEFL35p was coimmunoprecipitated with itself and ebolavirus VP35s but not with the viral nucleoprotein. Then the biological functions of mlEFL35p were analyzed by comparing it to ebolavirus VP35s. We found that the expression of mlEFL35p significantly inhibited human IFN-β promoter activity as well as VP35s. By contrast, expression of mlEFL35p did not support viral RNA transcription/replication and indeed slightly decrease the reporter gene expression in a minigenome assay. These results suggest that mlEFL35p potentially acts as an IFN antagonist but not a polymerase cofactor.",
author = "Tatsunari Kondoh and Rashid Manzoor and Naganori Nao and Junki Maruyama and Wakako Furuyama and Hiroko Miyamoto and Asako Shigeno and Makoto Kuroda and Keita Matsuno and Daisuke Fujikura and Masahiro Kajihara and Reiko Yoshida and Manabu Igarashi and Ayato Takada",
year = "2017",
month = "10",
day = "1",
doi = "10.1371/journal.pone.0186450",
language = "English (US)",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

TY - JOUR

T1 - Putative endogenous filovirus VP35-like protein potentially functions as an IFN antagonist but not a polymerase cofactor

AU - Kondoh, Tatsunari

AU - Manzoor, Rashid

AU - Nao, Naganori

AU - Maruyama, Junki

AU - Furuyama, Wakako

AU - Miyamoto, Hiroko

AU - Shigeno, Asako

AU - Kuroda, Makoto

AU - Matsuno, Keita

AU - Fujikura, Daisuke

AU - Kajihara, Masahiro

AU - Yoshida, Reiko

AU - Igarashi, Manabu

AU - Takada, Ayato

PY - 2017/10/1

Y1 - 2017/10/1

N2 - It has been proposed that some non-retroviral RNA virus genes are integrated into vertebrate genomes. Endogenous filovirus-like elements (EFLs) have been discovered in some mammalian genomes. However, their potential roles in ebolavirus infection are unclear. A filovirus VP35-like element (mlEFL35) is found in the little brown bat (Myotis lucifugus) genome. Putative mlEFL35-derived protein (mlEFL35p) contains nearly full-length amino acid sequences corresponding to ebolavirus VP35. Ebola virus VP35 has been shown to bind double-stranded RNA, leading to inhibition of type I interferon (IFN) production, and is also known as a viral polymerase cofactor that is essential for viral RNA transcription/replication. In this study, we transiently expressed mlEFL35p in human kidney cells and investigated its biological functions. We first found that mlEFL35p was coimmunoprecipitated with itself and ebolavirus VP35s but not with the viral nucleoprotein. Then the biological functions of mlEFL35p were analyzed by comparing it to ebolavirus VP35s. We found that the expression of mlEFL35p significantly inhibited human IFN-β promoter activity as well as VP35s. By contrast, expression of mlEFL35p did not support viral RNA transcription/replication and indeed slightly decrease the reporter gene expression in a minigenome assay. These results suggest that mlEFL35p potentially acts as an IFN antagonist but not a polymerase cofactor.

AB - It has been proposed that some non-retroviral RNA virus genes are integrated into vertebrate genomes. Endogenous filovirus-like elements (EFLs) have been discovered in some mammalian genomes. However, their potential roles in ebolavirus infection are unclear. A filovirus VP35-like element (mlEFL35) is found in the little brown bat (Myotis lucifugus) genome. Putative mlEFL35-derived protein (mlEFL35p) contains nearly full-length amino acid sequences corresponding to ebolavirus VP35. Ebola virus VP35 has been shown to bind double-stranded RNA, leading to inhibition of type I interferon (IFN) production, and is also known as a viral polymerase cofactor that is essential for viral RNA transcription/replication. In this study, we transiently expressed mlEFL35p in human kidney cells and investigated its biological functions. We first found that mlEFL35p was coimmunoprecipitated with itself and ebolavirus VP35s but not with the viral nucleoprotein. Then the biological functions of mlEFL35p were analyzed by comparing it to ebolavirus VP35s. We found that the expression of mlEFL35p significantly inhibited human IFN-β promoter activity as well as VP35s. By contrast, expression of mlEFL35p did not support viral RNA transcription/replication and indeed slightly decrease the reporter gene expression in a minigenome assay. These results suggest that mlEFL35p potentially acts as an IFN antagonist but not a polymerase cofactor.

UR - http://www.scopus.com/inward/record.url?scp=85031787096&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031787096&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0186450

DO - 10.1371/journal.pone.0186450

M3 - Article

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

M1 - e0186450

ER -