HOST ADAPTIVE IMMUNITY MODULATES CHIKUNGUNYA DISEASE MANIFESTATION

Abstract

CHIKUNGUNYA VIRUS (CHIKV) IS AN ALPHAVIRUS THAT IS RESPONSIBLE FOR CAUSING CHRONIC AND INCAPACITATING ARTHRALGIA IN HUMANS. DESPITE THE EXTENSIVE EFFORTS IN UNDERSTANDING CHIKV IMMUNOPATHOGENESIS, THE ROLE OF THE ADAPTIVE IMMUNITY REMAINS ELUSIVE. IN THIS STUDY, THE ROLE OF THE ADAPTIVE IMMUNITY IN CHIKV INFECTION WAS ELUCIDATED USING THE JOINT INFLAMMATION MOUSE MODEL. RESULTS DEMONSTRATED THAT CD4+ T CELLS WERE PATHOGENIC, WHEREAS B CELLS AND ANTI-CHIKV ANTIBODIES WERE ESSENTIAL FOR CHIKV CLEARANCE. HOWEVER, ANTIBODIES AT SUB-NEUTRALIZING CONCENTRATIONS CAN ENHANCE VIRUS INFECTION AND EXACERBATE DISEASE SEVERITY. CHIKV INFECTION IN THE PRESENCE OF CHIKV-SPECIFIC ANTIBODIES WAS EXPLORED IN PRIMARY HUMAN IMMUNE CELLS. A SIGNIFICANT INCREASE IN INFECTIVITY WAS OBSERVED AND BLOCKING OF FC RECEPTORS ABROGATED THIS ENHANCEMENT. ADULT MICE HAD HIGHER VIREMIA AND GREATER JOINT INFLAMMATION WHEN INFECTION WAS PERFORMED IN THE PRESENCE OF SUB-NEUTRALIZING CONCENTRATIONS OF CHIKV-SPECIFIC ANTIB