James Crowe
Faculty Member
Last active: 3/31/2019

Pathogenic Chikungunya Virus Evades B Cell Responses to Establish Persistence.

Hawman DW, Fox JM, Ashbrook AW, May NA, Schroeder KMS, Torres RM, Crowe JE, Dermody TS, Diamond MS, Morrison TE
Cell Rep. 2016 16 (5): 1326-1338

PMID: 27452455 · PMCID: PMC5003573 · DOI:10.1016/j.celrep.2016.06.076

Chikungunya virus (CHIKV) and related alphaviruses cause epidemics of acute and chronic musculoskeletal disease. To investigate the mechanisms underlying the failure of immune clearance of CHIKV, we studied mice infected with an attenuated CHIKV strain (181/25) and the pathogenic parental strain (AF15561), which differ by five amino acids. Whereas AF15561 infection of wild-type mice results in viral persistence in joint tissues, 181/25 is cleared. In contrast, 181/25 infection of μMT mice lacking mature B cells results in viral persistence in joint tissues, suggesting that virus-specific antibody is required for clearance of infection. Mapping studies demonstrated that a highly conserved glycine at position 82 in the A domain of the E2 glycoprotein impedes clearance and neutralization of multiple CHIKV strains. Remarkably, murine and human antibodies targeting E2 domain B failed to neutralize pathogenic CHIKV strains efficiently. Our data suggest that pathogenic CHIKV strains evade E2 domain-B-neutralizing antibodies to establish persistence.

Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

MeSH Terms (13)

Amino Acids Animals Antibodies, Monoclonal Antibodies, Neutralizing Antibodies, Viral B-Lymphocytes Chikungunya Fever Chikungunya virus Glycoproteins Humans Mice Mice, Inbred C57BL Viral Envelope Proteins

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