Convergent Antibody Signatures in Human Dengue

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• 作者：Poornima Parameswaran¹ ; ² ; Yi Liu³ ; ⁵ ; Krishna M. Roskin² ; Katherine K.L. Jackson² ; Vaishali P. Dixit² ; Ji-Yeun Lee² ; Karen L. Artiles² ; Simona Zompi¹ ; Maria José ; Vargas⁶ ; Birgitte B. Simen⁷ ; Bozena Hanczaruk⁷ ; Kim R. McGowan⁷ ; Muhammad A. Tariq⁸ ; Nader Pourmand⁸ ; Daphne Koller³ ; Angel Balmaseda⁶ ; Scott D. Boyd² ; ⁹ ; ^{sboyd1@stanford.edu} ; Eva Harris¹ ; ⁹ ; ^{eharris@berkeley.edu} ; Andrew Z. Fire² ; ⁴ ; ⁹ ; ^{afire@stanford.edu}
• 刊名：Cell Host Microbe
• 出版年：2013
• 出版时间：12 June, 2013
• 年：2013
• 卷：13
• 期：6
• 页码：691-700
• 全文大小：3461 K

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Summary

Dengue is the most prevalent mosquito-borne viral disease in humans, and the lack of early prognostics, vaccines, and therapeutics contributes to immense disease burden. To identify patterns that could be used for sequence-based monitoring of the antibody response to dengue, we examined antibody heavy-chain gene rearrangements in longitudinal peripheral blood samples from 60 dengue patients. Comparing signatures between acute dengue, postrecovery, and healthy samples, we found increased expansion of B cell clones in acute dengue patients, with higher overall clonality in secondary infection. Additionally, we observed consistent antibody sequence features in acute dengue in the highly variable major antigen-binding determinant, complementarity-determining region 3 (CDR3), with specific CDR3 sequences highly enriched in acute samples compared to postrecovery, healthy, or non-dengue samples. Dengue thus provides a striking example of a human viral infection where convergent immune signatures can be identified in multiple individuals. Such signatures could facilitate surveillance of immunological memory in communities.