Pathogenic Chikungunya Virus Evades B Cell Responses to Establish Persistence

作者：Hawman David W; Fox Julie M; Ashbrook Alison W; May Nicholas A; Schroeder Kristin M S; Torres Raul M; Crowe James E Jr; Dermody Terence S; Diamond Michael S; Morrison Thomas E

来源：Cell Reports, 2016, 16(5): 1326-1338.

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 mu MT 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.

• 出版日期2016-8-2