Convergent Antibody Signatures in Human Dengue

Poornima Parameswaran, Yi Liu, Krishna M. Roskin, Katherine K.L. Jackson, Vaishali P. Dixit,  Ji-Yeun Lee, Karen L. Artiles, Simona Zompi, Maria Jose´ Vargas, Birgitte B. Simen, Bozena Hanczaruk, Kim R. McGowan, Muhammad A. Tariq, Nader Pourmand, Daphne Koller, Angel Balmaseda, Scott D. Boyd, Eva Harris, and Andrew Z. Fire. Cell Host & Microbe. 13, 691-700 (2013)

Speaker: Po-Jung Fu (傅柏蓉)                                     Time: 13:00~14:00, Nov. 20, 2013.

Commentator: Dr. Trai-Ming Yeh (葉才明 老師)       Place: Room 601

Abstract:

    Dengue virus (DENV), belonging to Flaviviridae, is a mosquito-borne ssRNA virus, which causes about 300 million infections annually. DENV consisting of four serotypes could cause clinical manifestations from asymptomatic infection to lethal dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Currently, there are no vaccines or anti-viral treatments available for DV infections, also lack of prognostic biomarker, thus imposing a major burden on health care system [1]. High throughput sequencing of antibody genes of the patients facilitates the development of immunoglobulin heavy chain signatures in humans [2]. To reveal the signatures of antibody heavy chain of 60 dengue patients, the authors employed the barcoded multi-primers to amplify the hyper-variable region of the antibody heavy-chain genes by PCR, and followed by next generation sequencing. Complementarity-determining region 3 (CDR3) in antibody heavy-chain genes is the major determinant of antibody specificity, which shows diverse signatures among normal individuals. The physicochemicle profiles (molecular weight, isoelectric pH and hydrophilicity scores) of each amino acid are similar in CDR3s, which play an important role in antigen recognition. Interestingly, the authors revealed the convergent CDR3 signatures in the dengue patients, suggesting when the host encounters pathogens including DENV, CDR3 region of the heavy-chain genes becomes convergent through the modification process, such as affinity maturation of B cell. In conclusion, this paper provides a striking example that similar antibody signatures can be identified in a human infectious disease. Moreover, these convergent antibody signatures in dengue patients could be a potential indicator for diagnosis or for tracking and surveying exposure to DENV in endemic communities.

References:

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2. Boyd S.D., Marshall E.L., Merker J.D., Maniar J.M., Zhang L.N., Sahaf B., Jones C.D., Simen B.B., Hanczaruk B., Nguyen K.D., Nadeau K.C., Egholm M.,Miklos D.B., Zehnder J.L., Fire A.Z.(2009). Measurement and clinical monitoring of human lymphocyte clonality by massively parallel VDJ pyrosequencing. Sci. Transl. Med. 1, 12ra23.