Mosquito Rasputin interacts with chikungunya virus nsP3 and determines the infection rate in Aedes albopictus

Autor: Fros, Jelke J, Geertsema, Corinne, Zouache, Karima, Baggen, Jim, Domeradzka, Natalia, van Leeuwen, Daniël M, Flipse, Jacky, Vlak, Just M, Failloux, Anna-Bella, Pijlman, Gorben P, LS Virologie, I&I SIB1, Infection & Immunity
Přispěvatelé: Laboratory of Virology, Wageningen University and Research [Wageningen] (WUR), Arbovirus et Insectes Vecteurs - Arboviruses and Insect Vectors, Institut Pasteur [Paris], LS Virologie, I&I SIB1, Infection & Immunity, Institut Pasteur [Paris] (IP)
Jazyk: angličtina
Rok vydání: 2015
Předmět:
MESH: Sequence Analysis
DNA
viruses
MESH: Insect Vectors/virology
Laboratory of Virology
Viral Nonstructural Proteins
MESH: Chikungunya virus/physiology
medicine.disease_cause
G3BP
Aedes
Rasputin
Protein Interaction Mapping
MESH: Animals
Chikungunya
MESH: Viral Nonstructural Proteins/metabolism
virus diseases
PE&RC
Aedes albopictus
3. Good health
Infectious Diseases
Host-Pathogen Interactions
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Insect Proteins
MESH: Insect Proteins/metabolism
Chikungunya virus
Protein Binding
Molecular Sequence Data
Alphavirus
Biology
Virus
Laboratorium voor Virologie
Stress granule
parasitic diseases
medicine
Gene silencing
Animals
MESH: Americas
MESH: Protein Binding
MESH: Molecular Sequence Data
MESH: Aedes/virology
Research
fungi
MESH: Host-Pathogen Interactions
Sequence Analysis
DNA
biology.organism_classification
Virology
Insect Vectors
nsP3
Togaviridae
Parasitology
Americas
Physical Chemistry and Soft Matter
Vector competence
Zdroj: Parasites and Vectors
Parasites and Vectors, BioMed Central, 2015, 8 (1), pp.464. ⟨10.1186/s13071-015-1070-4⟩
Parasites & Vectors
Parasites & Vectors 8 (2015) 1
Parasites & Vectors, 8(1)
Parasites & Vectors, 2015, 8 (1), pp.464. ⟨10.1186/s13071-015-1070-4⟩
Parasites & Vectors, 8. BioMed Central
ISSN: 1756-3305
DOI: 10.1186/s13071-015-1070-4⟩
Popis: BACKGROUND: Chikungunya virus (CHIKV) is an arthritogenic alphavirus (family Togaviridae), transmitted by Aedes species mosquitoes. CHIKV re-emerged in 2004 with multiple outbreaks worldwide and recently reached the Americas where it has infected over a million individuals in a rapidly expanding epidemic. While alphavirus replication is well understood in general, the specific function (s) of non-structural protein nsP3 remain elusive. CHIKV nsP3 modulates the mammalian stress response by preventing stress granule formation through sequestration of G3BP. In mosquitoes, nsP3 is a determinant of vector specificity, but its functional interaction with mosquito proteins is unclear. METHODS: In this research we studied the domains required for localization of CHIKV nsP3 in insect cells and demonstrated its molecular interaction with Rasputin (Rin), the mosquito homologue of G3BP. The biological involvement of Rin in CHIKV infection was investigated in live Ae. albopictus mosquitoes. RESULTS: In insect cells, nsP3 localized as cytoplasmic granules, which was dependent on the central domain and the C-terminal variable region but independent of the N-terminal macrodomain. Ae. albopictus Rin displayed a diffuse, cytoplasmic localization, but was effectively sequestered into nsP3-granules upon nsP3 co-expression. Site-directed mutagenesis showed that the Rin-nsP3 interaction involved the NTF2-like domain of Rin and two conserved TFGD repeats in the C-terminal variable domain of nsP3. Although in vitro silencing of Rin did not impact nsP3 localization or CHIKV replication in cell culture, Rin depletion in vivo significantly decreased the CHIKV infection rate and transmissibility in Ae.albopictus. CONCLUSIONS: We identified the nsP3 hypervariable C-terminal domain as a critical factor for granular localization and sequestration of mosquito Rin. Our study offers novel insight into a conserved virus-mosquito interaction at the molecular level, and reveals a strong proviral role for G3BP homologue Rin in live mosquitoes, making the nsP3-Rin interaction a putative target to interfere with the CHIKV transmission cycle.
Databáze: OpenAIRE
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