Orbivirus NS4 Proteins Play Multiple Roles to Dampen Cellular Responses

Non-structural protein 4 (NS4) of insect-borne and tick-borne orbiviruses is encoded by genome segment 9, from a secondary open reading frame. Though a protein dispensable for bluetongue virus (BTV) replication, it has been shown to counter the interferon response in cells infected with BTV or Afric...

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Published inViruses Vol. 15; no. 9; p. 1908
Main Authors Mohd Jaafar, Fauziah, Belhouchet, Mourad, Monsion, Baptiste, Bell-Sakyi, Lesley, Mertens, Peter P. C., Attoui, Houssam
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 12.09.2023
MDPI
Subjects
African horse sickness
African horse sickness virus
Animals
antagonists
Apoptosis
Bluetongue
Bluetongue virus
Bluetongue virus - genetics
Caspase 3
Cloning
Deletion mutant
E3L protein
Enzymes
genome
Genomes
Great Island virus
Health aspects
innate responses
Interferon
Interferon Type I
interferons
Life Sciences
Mammalian cells
Mammals
Microbiology and Parasitology
mutants
NS4
orbivirus
Orbivirus - genetics
pathogenesis
Physiological aspects
Plasmids
Proteins
Reoviruses
St. Croix River virus
Thogotovirus
Vaccinia virus
viral nonstructural proteins
Viral proteins
Virology
virulence
Virulence factors
Virus research
Viruses
France
United States > US
Great Island virus
orbivirus
St. Croix River virus
bluetongue virus
innate responses
NS4
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Abstract Non-structural protein 4 (NS4) of insect-borne and tick-borne orbiviruses is encoded by genome segment 9, from a secondary open reading frame. Though a protein dispensable for bluetongue virus (BTV) replication, it has been shown to counter the interferon response in cells infected with BTV or African horse sickness virus. We further explored the functional role(s) of NS4 proteins of BTV and the tick-borne Great Island virus (GIV). We show that NS4 of BTV or GIV helps an E3L deletion mutant of vaccinia virus to replicate efficiently in interferon-treated cells, further confirming the role of NS4 as an interferon antagonist. Our results indicate that ectopically expressed NS4 of BTV localised with caspase 3 within the nucleus and was found in a protein complex with active caspase 3 in a pull-down assay. Previous studies have shown that pro-apoptotic caspases (including caspase 3) suppress type I interferon response by cleaving mediators involved in interferon signalling. Our data suggest that orbivirus NS4 plays a role in modulating the apoptotic process and/or regulating the interferon response in mammalian cells, thus acting as a virulence factor in pathogenesis.
AbstractList Non-structural protein 4 (NS4) of insect-borne and tick-borne orbiviruses is encoded by genome segment 9, from a secondary open reading frame. Though a protein dispensable for bluetongue virus (BTV) replication, it has been shown to counter the interferon response in cells infected with BTV or African horse sickness virus. We further explored the functional role(s) of NS4 proteins of BTV and the tick-borne Great Island virus (GIV). We show that NS4 of BTV or GIV helps an E3L deletion mutant of vaccinia virus to replicate efficiently in interferon-treated cells, further confirming the role of NS4 as an interferon antagonist. Our results indicate that ectopically expressed NS4 of BTV localised with caspase 3 within the nucleus and was found in a protein complex with active caspase 3 in a pull-down assay. Previous studies have shown that pro-apoptotic caspases (including caspase 3) suppress type I interferon response by cleaving mediators involved in interferon signalling. Our data suggest that orbivirus NS4 plays a role in modulating the apoptotic process and/or regulating the interferon response in mammalian cells, thus acting as a virulence factor in pathogenesis.
Non-structural protein 4 (NS4) of insect-borne and tick-borne orbiviruses is encoded by genome segment 9, from a secondary open reading frame. Though a protein dispensable for bluetongue virus (BTV) replication, it has been shown to counter the interferon response in cells infected with BTV or African horse sickness virus. We further explored the functional role(s) of NS4 proteins of BTV and the tick-borne Great Island virus (GIV). We show that NS4 of BTV or GIV helps an E3L deletion mutant of vaccinia virus to replicate efficiently in interferon-treated cells, further confirming the role of NS4 as an interferon antagonist. Our results indicate that ectopically expressed NS4 of BTV localised with caspase 3 within the nucleus and was found in a protein complex with active caspase 3 in a pull-down assay. Previous studies have shown that pro-apoptotic caspases (including caspase 3) suppress type I interferon response by cleaving mediators involved in interferon signalling. Our data suggest that orbivirus NS4 plays a role in modulating the apoptotic process and/or regulating the interferon response in mammalian cells, thus acting as a virulence factor in pathogenesis.Non-structural protein 4 (NS4) of insect-borne and tick-borne orbiviruses is encoded by genome segment 9, from a secondary open reading frame. Though a protein dispensable for bluetongue virus (BTV) replication, it has been shown to counter the interferon response in cells infected with BTV or African horse sickness virus. We further explored the functional role(s) of NS4 proteins of BTV and the tick-borne Great Island virus (GIV). We show that NS4 of BTV or GIV helps an E3L deletion mutant of vaccinia virus to replicate efficiently in interferon-treated cells, further confirming the role of NS4 as an interferon antagonist. Our results indicate that ectopically expressed NS4 of BTV localised with caspase 3 within the nucleus and was found in a protein complex with active caspase 3 in a pull-down assay. Previous studies have shown that pro-apoptotic caspases (including caspase 3) suppress type I interferon response by cleaving mediators involved in interferon signalling. Our data suggest that orbivirus NS4 plays a role in modulating the apoptotic process and/or regulating the interferon response in mammalian cells, thus acting as a virulence factor in pathogenesis.
Audience Academic
Author Monsion, Baptiste
Mertens, Peter P. C.
Mohd Jaafar, Fauziah
Belhouchet, Mourad
Bell-Sakyi, Lesley
Attoui, Houssam
AuthorAffiliation 1 UMR1161 VIROLOGIE, INRAE, Ecole Nationale Vétérinaire d’Alfort, ANSES, Université Paris-Est, 94700 Maisons-Alfort, France; baptiste.monsion@vet-alfort.fr
2 Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, Oxford OX3 7BN, UK; mourad.belhouchet@outlook.com
4 One Virology, The Wolfson Centre for Global Virus Research, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, Leicestershire LE12 5RD, UK; peter.mertens@nottingham.ac.uk
3 Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, 146 Brownlow Hill, Liverpool L3 5RF, UK; lsakyi@liverpool.ac.uk
AuthorAffiliation_xml – name: 4 One Virology, The Wolfson Centre for Global Virus Research, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, Leicestershire LE12 5RD, UK; peter.mertens@nottingham.ac.uk
– name: 2 Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, Oxford OX3 7BN, UK; mourad.belhouchet@outlook.com
– name: 1 UMR1161 VIROLOGIE, INRAE, Ecole Nationale Vétérinaire d’Alfort, ANSES, Université Paris-Est, 94700 Maisons-Alfort, France; baptiste.monsion@vet-alfort.fr
– name: 3 Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, 146 Brownlow Hill, Liverpool L3 5RF, UK; lsakyi@liverpool.ac.uk
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  surname: Mohd Jaafar
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Issue 9
Keywords Great Island virus
orbivirus
St. Croix River virus
bluetongue virus
innate responses
NS4
Language English
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Snippet Non-structural protein 4 (NS4) of insect-borne and tick-borne orbiviruses is encoded by genome segment 9, from a secondary open reading frame. Though a protein...
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StartPage 1908
SubjectTerms African horse sickness
African horse sickness virus
Animals
antagonists
Apoptosis
Bluetongue
Bluetongue virus
Bluetongue virus - genetics
Caspase 3
Cloning
Deletion mutant
E3L protein
Enzymes
genome
Genomes
Great Island virus
Health aspects
innate responses
Interferon
Interferon Type I
interferons
Life Sciences
Mammalian cells
Mammals
Microbiology and Parasitology
mutants
NS4
orbivirus
Orbivirus - genetics
pathogenesis
Physiological aspects
Plasmids
Proteins
Reoviruses
St. Croix River virus
Thogotovirus
Vaccinia virus
viral nonstructural proteins
Viral proteins
Virology
virulence
Virulence factors
Virus research
Viruses
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Title Orbivirus NS4 Proteins Play Multiple Roles to Dampen Cellular Responses
URI https://www.ncbi.nlm.nih.gov/pubmed/37766314
https://www.proquest.com/docview/2869651049
https://www.proquest.com/docview/2870137362
https://www.proquest.com/docview/3040483717
https://hal.inrae.fr/hal-04213414
https://pubmed.ncbi.nlm.nih.gov/PMC10535134
https://doaj.org/article/707490d10f164c6a93357643fd2b7fb1
Volume 15
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