Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection

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Neutralizing antibodies (nAbs) represent a key principle of antiviral immunity. Protective vaccines aim at inducing nAbs to prevent viral infection, and infusion of nAbs in convalescent patient serum can offer a potent antiviral therapy. Certain viruses, however, have found ways to evade nAb control. Amongst them are high-risk pathogens of the arenavirus family such as Lassa virus (LASV), which is a frequent cause of hemorrhagic fever in West Africa. Here we unveil the molecular strategy by which arenaviruses escape antibody neutralization and avoid efficient immune control. We show that their surface is decorated with sugar moieties, serving to shield the virus against the neutralizing effect of the host’s antibodies. This immune evasion strategy differs from those described for other viruses, in which sugars impair primarily the induction of antibodies or allow for viral mutational escape. The arenavirus sugar coat renders the host nAb response inefficient and as a consequence thereof, the host fails to promptly control the infection. Our results offer a compelling explanation for the long history of failures in trying to make a nAb-based vaccine against LASV or in using convalescent serum for therapy. These mechanistic insights will support vaccine development efforts against arenaviruses such as LASV.

Vyšlo v časopise: Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005276
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005276

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