Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease.
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008517 |
| _version_ | 1819028126640898048 |
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| author | Laura A Powell Julie M Fox Nurgun Kose Arthur S Kim Mahsa Majedi Robin Bombardi Robert H Carnahan James C Slaughter Thomas E Morrison Michael S Diamond James E Crowe |
| author_facet | Laura A Powell Julie M Fox Nurgun Kose Arthur S Kim Mahsa Majedi Robin Bombardi Robert H Carnahan James C Slaughter Thomas E Morrison Michael S Diamond James E Crowe |
| author_sort | Laura A Powell |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T05:53:25Z |
| format | Article |
| id | doaj.art-fc27c479d8374c239eef85a153e5780e |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-21T05:53:25Z |
| publishDate | 2020-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-fc27c479d8374c239eef85a153e5780e2022-12-21T19:13:55ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-05-01165e100851710.1371/journal.ppat.1008517Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease.Laura A PowellJulie M FoxNurgun KoseArthur S KimMahsa MajediRobin BombardiRobert H CarnahanJames C SlaughterThomas E MorrisonMichael S DiamondJames E CroweRoss 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.https://doi.org/10.1371/journal.ppat.1008517 |
| spellingShingle | Laura A Powell Julie M Fox Nurgun Kose Arthur S Kim Mahsa Majedi Robin Bombardi Robert H Carnahan James C Slaughter Thomas E Morrison Michael S Diamond James E Crowe Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease. PLoS Pathogens |
| title | Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease. |
| title_full | Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease. |
| title_fullStr | Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease. |
| title_full_unstemmed | Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease. |
| title_short | Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease. |
| title_sort | human monoclonal antibodies against ross river virus target epitopes within the e2 protein and protect against disease |
| url | https://doi.org/10.1371/journal.ppat.1008517 |
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