Cytokine profile, neutralisation potential and viral replication dynamics in sera of chikungunya patients in India: a cross-sectional study

Naren Babu; Shakuntala Mahilkar; Anup Jayaram; Sylvester Agha Ibemgbo; Garvita Mathur; Ujwal Shetty; Robin Sudandiradas; P Sanjai Kumar; Sharad Singh; Sweta Smita Pani; Piya Paul Mudgal; Jayanthi S Shastri; Sachee Agarwal; P K Ratho; Baijayantimala Mishra; Soma Chattopadhyay; Anitha Jagadesh; Sujatha Sunil

doi:10.1016/j.lansea.2023.100269

Cytokine profile, neutralisation potential and viral replication dynamics in sera of chikungunya patients in India: a cross-sectional study

Lancet Reg Health Southeast Asia. 2023 Sep 1:19:100269. doi: 10.1016/j.lansea.2023.100269. eCollection 2023 Dec.

Authors

Naren Babu¹, Shakuntala Mahilkar², Anup Jayaram¹, Sylvester Agha Ibemgbo², Garvita Mathur², Ujwal Shetty¹, Robin Sudandiradas¹, P Sanjai Kumar³, Sharad Singh^{3

4}, Sweta Smita Pani³, Piya Paul Mudgal¹, Jayanthi S Shastri⁵, Sachee Agarwal⁵, P K Ratho⁶, Baijayantimala Mishra⁷, Soma Chattopadhyay³, Anitha Jagadesh¹, Sujatha Sunil²

Affiliations

¹ Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka 576104, India.
² Vector-Borne Diseases Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi 110067, India.
³ Institute of Life Sciences (ILS), Nalco Square, Bhubaneswar, Orissa 751023, India.
⁴ KIIT School of Biotechnology, Bhubaneswar, Orissa 751023, India.
⁵ Department of Microbiology, TNMC and BYL, Nair Charitable Hospital, Mumbai, Maharashtra 400008, India.
⁶ Department of Virology, Post-Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
⁷ Department of Microbiology, All India Institute of Medical Sciences (AIIMS), Bhubaneshwar 751019, India.

Abstract

Background: Chikungunya disease (CHIKD) is a threat to global health, as it impairs the quality of life of an infected individual ranging from months to years. A systematic evaluation of the serological, virological, and immunological aspects of the circulating viruses and their impact on the host response is imperative for better understanding of the evolving disease dynamics.

Methods: Serum samples were collected from 196 acute CHIKD patients from ten tertiary care hospitals across India during 2016-2021. Out of 196 patients, paired convalescent samples were collected from 51 patients (one-month post-onset of symptoms). The serum samples were profiled for cytokines and neutralisation capacity. Further, chikungunya virus (CHIKV) was isolated from the acute sera and the replication kinetics of the clinical isolates was evaluated.

Findings: Serological analysis indicated that neutralisation could be correlated to seroconversion in the convalescent phase but not found significant in acute phase. In the acute phase samples, there was a correlation between elevated serum levels of IFN-γ, IP-10, MCP-1 and MIG and disease severity. During convalescent phase, pro-inflammatory markers such as IL-6, IL-1β, IL-9 and IP-10 were found to be elevated with a corresponding decline in the secretion of anti-inflammatory cytokines such as IL-4 and IL-10, which correlated with persistent arthralgia. Analysis of replication of the clinical isolates revealed that 68.4% of viruses were fast-growing in the Vero cells (cytopathic effect [CPE] observed within 24 h post-infection), and their corresponding acute serum samples showed an elevated secretion of IFN-α, IL-1RA, IL-17F, IL-9, MCP-1 and MIP-1α.

Interpretation: This study provides an important overview of neutralisation capabilities and cytokine responses along with virus pathogenesis associated with CHIKV infections in India.

Funding: Biotechnology Industry Research Assistance Council (BIRAC).

Keywords: Acute infection; Arthralgia; Chikungunya disease; Chikungunya virus; Inflammatory cytokine; Virus neutralization; Virus replication.