Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease.
PLoS Pathog
; 16(5): e1008517, 2020 05.
Article
en En
| MEDLINE
| ID: mdl-32365139
ABSTRACT
Ross River fever is a mosquito-transmitted viral disease that is endemic to Australia and the surrounding Pacific Islands. Ross River virus (RRV) belongs to the arthritogenic group of alphaviruses, which largely cause disease characterized by debilitating polyarthritis, rash, and fever. There is no specific treatment or licensed vaccine available, and the mechanisms of protective humoral immunity in humans are poorly understood. Here, we describe naturally occurring human mAbs specific to RRV, isolated from subjects with a prior natural infection. These mAbs potently neutralize RRV infectivity in cell culture and block infection through multiple mechanisms, including prevention of viral attachment, entry, and fusion. Some of the most potently neutralizing mAbs inhibited binding of RRV to Mxra8, a recently discovered alpahvirus receptor. Epitope mapping studies identified the A and B domains of the RRV E2 protein as the major antigenic sites for the human neutralizing antibody response. In experiments in mice, these mAbs were protective against cinical disease and reduced viral burden in multiple tissues, suggesting a potential therapeutic use for humans.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Virus del Río Ross
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Proteínas del Envoltorio Viral
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Infecciones por Alphavirus
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Proteínas de la Cápside
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Anticuerpos Neutralizantes
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Anticuerpos Monoclonales
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Anticuerpos Antivirales
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Epítopos
Límite:
Animals
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Female
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Humans
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Middle aged
Idioma:
En
Año:
2020
Tipo del documento:
Article