Defining the impact of Getah virus envelope protein glycosylation site mutations on viral replication, host adaptation, virulence, and immune evasion
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Le résumé fourni par la source
The N-linked glycosylation of alphavirus envelope proteins plays critical roles in glycoprotein folding, host-receptor interactions, immune evasion, and pathogenicity. Getah virus (GETV) has two putative N-linked glycosylation sites (N-200 and N-262) in the E2 and one (N-141) in E1. We generated seven glycosylation-deficient mutants and evaluated their fitness across mammalian cells, mosquitoes, and mouse models. Loss of glycosylation at E2 N-262 or E1 N-141 enhanced in vitro replication and replication efficiency in mosquitoes, while E2 N-200 glycosylation-deficient mutants retained parental replication capacity in vitro but exhibited accelerated mosquito colonization. Despite these gains, glycan loss reduced viral adsorption/entry in selected settings and decreased measurable virion binding to MXRA8 and LDLR in vitro, while single-site E2 glycan mutants exhibited increased heparin sensitivity/affinity, indicating altered utilization of glycosaminoglycan attachment pathways. In vivo, all mutants remained lethal in 3-day-old mice but showed age-dependent attenuation in 10-day-old mice. Notably, E1 N141-deficient mutant induced no clinical symptoms and exhibited reduced viremia and tissue viral loads. Glycan ablation increased susceptibility to neutralization without impairing induction of neutralizing antibodies. Strikingly, E2 mutants rapidly reacquired glycosylation during in vivo replication, indicating strong evolutionary selection for these sites. Together, our data support an evolutionary trade-off in which GETV envelope glycans-particularly the epidemic-lineage-associated E2-N262 glycan-optimize overall fitness by balancing replication/transmission efficiency with humoral immune evasion.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Defining the impact of Getah virus envelope protein glycosylation site mutations on viral replication, host adaptation, virulence, and immune evasion
- Date Crossref
- 02/04/2026
- Éditeur
- Public Library of Science (PLoS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Guangxi University pays non établi dans la noticeUniversité ou école supérieure
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Guangxi Veterinary Research Institute pays non établi dans la noticeStructure de recherche
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Guangxi Center for Disease Prevention and Control pays non établi dans la noticeOrganisme public
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College of Animal Science and Technology Laboratory of Animal infectious Diseases and molecular Immunology pays non établi dans la noticeUniversité ou école supérieure
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Guangxi Key Laboratory of Animal Reproduction pays non établi dans la noticeStructure de recherche
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Guangxi Zhuang Autonomous Region Engineering Research Center of Veterinary Biologics pays non établi dans la noticeStructure de recherche
Guangxi University, Guangxi Veterinary Research Institute et Guangxi Center for Disease Prevention and Control, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.