
Full text loading...
Financial support: This study was supported by grants from the Department of Biotechnology (Grant number: BT/PR14725/AGR/36/672/2010 to S. S.), Government of India; Department of Science and Technology (Grant number: DST/INT/JST/P-25/2014 to R. G. and S. S.), Government of India; and NIH (Grant number: R24AI120942 to S. W.). S. W. reports grants from National Institute of Health during the conduct of the study.
Authors’ addresses: Jaspreet Jain, Vector Borne Disease Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India, and Department of Human Retrovirology, Montreal Clinical Research Institute, Montreal, Canada, E-mail: [email protected]. Ankit Kumar, Vimal Narayanan, and Sujatha Sunil, Vector Borne Disease Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India, E-mails: [email protected], [email protected], and [email protected]. Navjot Kaur, Department of Microbiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India, E-mails: [email protected] and [email protected]. Sherry L. Haller, Shannan L. Rossi, Scott C. Weaver, Department of Microbiology and Immunology, Institute for Human Infections and Immunity, Centre for Tropical Diseases, University of Texas Medical Branch, Galveston, TX, E-mails: [email protected], [email protected], and [email protected]. Albert J. Auguste, Department of Microbiology and Immunology, Institute for Human Infections and Immunity, Centre for Tropical Diseases, University of Texas Medical Branch, Galveston, TX, and Department of Entomology, Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA, E-mail: [email protected]. Dilip Kumar, Department of Medicine, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India, E-mail: [email protected].
Abstract.
Chikungunya fever (CHIKF) is a major public health concern and is caused by chikungunya virus (CHIKV). In 2005, the virus was reintroduced into India, resulting in massive outbreaks in several parts of the country. During 2010 and 2016 outbreaks, we recruited 588 patients from a tertiary care hospital in New Delhi, India, during the acute phase of CHIKF; collected their blood and clinical data; and determined their arthralgic status 12 weeks post-onset of fever. We evaluated IgM/IgG CHIKV-binding antibodies and their neutralizing capacity, sequenced complete genomes of 21 CHIKV strains, and correlated mutations with patient sequelae status. We also performed infections in murine models using representative strains from each outbreak to evaluate differences in pathogenesis. Our screening and analysis revealed that patients of the 2016 outbreak developed earlier IgM and neutralizing antibody responses that were negatively correlated with sequelae, compared with 2010 patients. Mutations that correlated with human disease progression were also correlated with enhanced murine virulence and pathogenesis. Overall, our study suggests that the development of early neutralizing antibodies and sequence variation in clinical isolates are predictors of human sequelae.