Identification of a non-canonical G3BP-binding sequence in a Mayaro virus nsP3 hypervariable domain
Abstract
Ras-GTPase-activating SH3 domain-binding-proteins 1 (G3BP1) and 2 (G3BP2) are multifunctional RNA-binding proteins involved in stress granule nucleation, previously identified as essential cofactors of Old World alphaviruses. They are recruited to viral replication complexes formed by the Chikungunya virus (CHIKV), Semliki Forest virus (SFV), and Sindbis virus (SINV) via an interaction with a duplicated FGxF motif conserved in the hypervariable domain (HVD) of virus-encoded nsP3. According to mutagenesis studies, this FGxF duplication is strictly required for G3BP binding and optimal viral growth. Contrasting with this scenario, nsP3 encoded by Mayaro virus (MAYV), an arthritogenic virus grouped with Old World alphaviruses, contains a single canonical FGxF sequence. In light of this unusual feature, we questioned MAYV nsP3/G3BPs relationships. We report that G3BP1 and G3BP2 are both required for MAYV growth in human cells and bind nsP3 protein. In infected cells, they are recruited to nsP3-containing cytosolic foci and active replication complexes. Unexpectedly, deletion of the single FGxF sequence in MAYV nsP3 did not abolish these phenotypes. Using mutagenesis and in silico modeling, we identify an upstream FGAP amino acid sequence as an additional MAYV nsP3/G3BP interaction motif required for optimal viral infectivity. These results, therefore, highlight a non-conventional G3BP binding sequence in MAYV nsP3.
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BibTeX
@article{neyret2026identification,
title = {{Identification of a non-canonical G3BP-binding sequence in a Mayaro virus nsP3 hypervariable domain}},
author = {Aymeric Neyret and Eric Bernard and Olivier Aïqui-Reboul-Paviet and William Bakhache and Patrick Eldin and Laurent Chaloin and Laurence Briant},
journal = {Frontiers in Cellular and Infection Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fcimb.2022.958176},
url = {https://hal.science/hal-05471090v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Identification of a non-canonical G3BP-binding sequence in a Mayaro virus nsP3 hypervariable domain
AU - Aymeric Neyret
AU - Eric Bernard
AU - Olivier Aïqui-Reboul-Paviet
AU - William Bakhache
AU - Patrick Eldin
AU - Laurent Chaloin
AU - Laurence Briant
PY - 2026
DA - 2026/10/01
JO - Frontiers in Cellular and Infection Microbiology
DO - 10.3389/fcimb.2022.958176
UR - https://hal.science/hal-05471090v1
AB - Ras-GTPase-activating SH3 domain-binding-proteins 1 (G3BP1) and 2 (G3BP2) are multifunctional RNA-binding proteins involved in stress granule nucleation, previously identified as essential cofactors of Old World alphaviruses. They are recruited to viral replication complexes formed by the Chikungunya virus (CHIKV), Semliki Forest virus (SFV), and Sindbis virus (SINV) via an interaction with a duplicated FGxF motif conserved in the hypervariable domain (HVD) of virus-encoded nsP3. According to mutagenesis studies, this FGxF duplication is strictly required for G3BP binding and optimal viral growth. Contrasting with this scenario, nsP3 encoded by Mayaro virus (MAYV), an arthritogenic virus grouped with Old World alphaviruses, contains a single canonical FGxF sequence. In light of this unusual feature, we questioned MAYV nsP3/G3BPs relationships. We report that G3BP1 and G3BP2 are both required for MAYV growth in human cells and bind nsP3 protein. In infected cells, they are recruited to nsP3-containing cytosolic foci and active replication complexes. Unexpectedly, deletion of the single FGxF sequence in MAYV nsP3 did not abolish these phenotypes. Using mutagenesis and in silico modeling, we identify an upstream FGAP amino acid sequence as an additional MAYV nsP3/G3BP interaction motif required for optimal viral infectivity. These results, therefore, highlight a non-conventional G3BP binding sequence in MAYV nsP3.
SN - 2235-2988
ER -