Exploration of binary protein-protein interactions between tick-borne flaviviruses and Ixodes ricinus.


Journal

Parasites & vectors
ISSN: 1756-3305
Titre abrégé: Parasit Vectors
Pays: England
ID NLM: 101462774

Informations de publication

Date de publication:
06 Mar 2021
Historique:
received: 11 12 2020
accepted: 18 02 2021
entrez: 7 3 2021
pubmed: 8 3 2021
medline: 4 9 2021
Statut: epublish

Résumé

Louping ill virus (LIV) and tick-borne encephalitis virus (TBEV) are tick-borne flaviviruses that are both transmitted by the major European tick, Ixodes ricinus. Despite the importance of I. ricinus as an arthropod vector, its capacity to acquire and subsequently transmit viruses, known as vector competence, is poorly understood. At the molecular scale, vector competence is governed in part by binary interactions established between viral and cellular proteins within infected tick cells. To investigate virus-vector protein-protein interactions (PPIs), the entire set of open reading frames for LIV and TBEV was screened against an I. ricinus cDNA library established from three embryonic tick cell lines using yeast two-hybrid methodology (Y2H). PPIs revealed for each viral bait were retested in yeast by applying a gap repair (GR) strategy, and notably against the cognate protein of both viruses, to determine whether the PPIs were specific for a single virus or common to both. The interacting tick proteins were identified by automatic BLASTX, and in silico analyses were performed to expose the biological processes targeted by LIV and TBEV. For each virus, we identified 24 different PPIs involving six viral proteins and 22 unique tick proteins, with all PPIs being common to both viruses. According to our data, several viral proteins (pM, M, NS2A, NS4A, 2K and NS5) target multiple tick protein modules implicated in critical biological pathways. Of note, the NS5 and pM viral proteins establish PPI with several tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which are essential adaptor proteins at the nexus of multiple signal transduction pathways. We provide the first description of the TBEV/LIV-I. ricinus PPI network, and indeed of any PPI network involving a tick-borne virus and its tick vector. While further investigation will be needed to elucidate the role of each tick protein in the replication cycle of tick-borne flaviviruses, our study provides a foundation for understanding the vector competence of I. ricinus at the molecular level. Indeed, certain PPIs may represent molecular determinants of vector competence of I. ricinus for TBEV and LIV, and potentially for other tick-borne flaviviruses.

Sections du résumé

BACKGROUND BACKGROUND
Louping ill virus (LIV) and tick-borne encephalitis virus (TBEV) are tick-borne flaviviruses that are both transmitted by the major European tick, Ixodes ricinus. Despite the importance of I. ricinus as an arthropod vector, its capacity to acquire and subsequently transmit viruses, known as vector competence, is poorly understood. At the molecular scale, vector competence is governed in part by binary interactions established between viral and cellular proteins within infected tick cells.
METHODS METHODS
To investigate virus-vector protein-protein interactions (PPIs), the entire set of open reading frames for LIV and TBEV was screened against an I. ricinus cDNA library established from three embryonic tick cell lines using yeast two-hybrid methodology (Y2H). PPIs revealed for each viral bait were retested in yeast by applying a gap repair (GR) strategy, and notably against the cognate protein of both viruses, to determine whether the PPIs were specific for a single virus or common to both. The interacting tick proteins were identified by automatic BLASTX, and in silico analyses were performed to expose the biological processes targeted by LIV and TBEV.
RESULTS RESULTS
For each virus, we identified 24 different PPIs involving six viral proteins and 22 unique tick proteins, with all PPIs being common to both viruses. According to our data, several viral proteins (pM, M, NS2A, NS4A, 2K and NS5) target multiple tick protein modules implicated in critical biological pathways. Of note, the NS5 and pM viral proteins establish PPI with several tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which are essential adaptor proteins at the nexus of multiple signal transduction pathways.
CONCLUSION CONCLUSIONS
We provide the first description of the TBEV/LIV-I. ricinus PPI network, and indeed of any PPI network involving a tick-borne virus and its tick vector. While further investigation will be needed to elucidate the role of each tick protein in the replication cycle of tick-borne flaviviruses, our study provides a foundation for understanding the vector competence of I. ricinus at the molecular level. Indeed, certain PPIs may represent molecular determinants of vector competence of I. ricinus for TBEV and LIV, and potentially for other tick-borne flaviviruses.

Identifiants

pubmed: 33676573
doi: 10.1186/s13071-021-04651-3
pii: 10.1186/s13071-021-04651-3
pmc: PMC7937244
doi:

Substances chimiques

Arthropod Proteins 0
Viral Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

144

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/P024270/1
Pays : United Kingdom
Organisme : labex IBEID
ID : ANR-10-LABX-62-IBEID

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Auteurs

Manon Lemasson (M)

UMR 1161 Virologie Laboratoire de Santé Animale, ANSES, INRAE, Ecole Nationale Vétérinaire d'Alfort, Paris-Est Sup, Maisons-Alfort, France.

Grégory Caignard (G)

UMR 1161 Virologie Laboratoire de Santé Animale, ANSES, INRAE, Ecole Nationale Vétérinaire d'Alfort, Paris-Est Sup, Maisons-Alfort, France.

Yves Unterfinger (Y)

UMR 1161 Virologie Laboratoire de Santé Animale, ANSES, INRAE, Ecole Nationale Vétérinaire d'Alfort, Paris-Est Sup, Maisons-Alfort, France.

Houssam Attoui (H)

UMR 1161 Virologie Laboratoire de Santé Animale, ANSES, INRAE, Ecole Nationale Vétérinaire d'Alfort, Paris-Est Sup, Maisons-Alfort, France.

Lesley Bell-Sakyi (L)

Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.

Edouard Hirchaud (E)

Viral Genetic and Biosecurity Unit, Ploufragan-Plouzané-Niort Laboratory, ANSES, Ploufragan, France.

Sara Moutailler (S)

UMR BIPAR, Laboratoire de Santé Animale, ANSES, INRAE, Ecole Nationale Vétérinaire d'Alfort, Paris-Est Sup, Maisons-Alfort, France.

Nicholas Johnson (N)

Animal and Plant Health Agency (APHA), Addlestone, Surrey, UK.

Damien Vitour (D)

UMR 1161 Virologie Laboratoire de Santé Animale, ANSES, INRAE, Ecole Nationale Vétérinaire d'Alfort, Paris-Est Sup, Maisons-Alfort, France.

Jennifer Richardson (J)

UMR 1161 Virologie Laboratoire de Santé Animale, ANSES, INRAE, Ecole Nationale Vétérinaire d'Alfort, Paris-Est Sup, Maisons-Alfort, France.

Sandrine A Lacour (SA)

UMR 1161 Virologie Laboratoire de Santé Animale, ANSES, INRAE, Ecole Nationale Vétérinaire d'Alfort, Paris-Est Sup, Maisons-Alfort, France. sandrine.lacour@anses.fr.

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