Convergent Antibody Signatures in Human Dengue

被引:195
作者
Parameswaran, Poornima [1 ,2 ]
Liu, Yi [3 ,5 ]
Roskin, Krishna M. [2 ]
Jackson, Katherine K. L. [2 ]
Dixit, Vaishali P. [2 ]
Lee, Ji-Yeun [2 ]
Artiles, Karen L. [2 ]
Zompi, Simona [1 ]
Jose Vargas, Maria [6 ]
Simen, Birgitte B. [7 ]
Hanczaruk, Bozena [7 ]
McGowan, Kim R. [7 ]
Tariq, Muhammad A. [8 ]
Pourmand, Nader [8 ]
Koller, Daphne [3 ]
Balmaseda, Angel [6 ]
Boyd, Scott D. [2 ]
Harris, Eva [1 ]
Fire, Andrew Z. [2 ,4 ]
机构
[1] Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis & Vaccinol, Berkeley, CA 94720 USA
[2] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA
[3] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA
[4] Stanford Univ, Dept Genet, Stanford, CA 94305 USA
[5] Stanford Univ, Sch Med, Biomed Informat Training Program, Stanford, CA 94305 USA
[6] Ctr Nacl Diagnos & Referencia, Lab Nacl Virol, Minist Hlth, Managua 16064, Nicaragua
[7] Roche Co, 454 Life Sci, Branford, CT 06405 USA
[8] Univ Calif Santa Cruz, Baskin Sch Engn, Santa Cruz, CA 95064 USA
关键词
CHRONIC LYMPHOCYTIC-LEUKEMIA; GENE REARRANGEMENTS; MONOCLONAL-ANTIBODIES; HEMORRHAGIC-FEVER; INFLUENZA-VIRUS; DIVERSITY; REGION; REPERTOIRE; ALIGNMENT; PATHOGENESIS;
D O I
10.1016/j.chom.2013.05.008
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:691 / 700
页数:10
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