Longitudinal [18F]FB-IL-2 PET Imaging to Assess the Immunopathogenicity of O'nyong-nyong Virus Infection

Longitudinal [18F]FB-IL-2 PET Imaging to Assess the Immunopathogenicity of O'nyong-nyong Virus Infection
Title:
Longitudinal [18F]FB-IL-2 PET Imaging to Assess the Immunopathogenicity of O'nyong-nyong Virus Infection
Other Titles:
Frontiers in immunology
Keywords:
Publication Date:
12 May 2020
Citation:
Chan Y-H, Teo T-H, Torres-Ruesta A, Hartimath SV, Chee RS-L, Khanapur S, Yong FF, Ramasamy B, Cheng P, Rajarethinam R, Robins EG, Goggi JL, Lum F-M, Carissimo G, Rénia L and Ng LFP (2020) Longitudinal [18F]FB-IL-2 PET Imaging to Assess the Immunopathogenicity of O’nyong-nyong Virus Infection. Front. Immunol. 11:894. doi: 10.3389/fimmu.2020.00894
Abstract:
O'nyong-nyong virus (ONNV) is an arthritogenic alphavirus that caused two large epidemics in 1959 and 1996, affecting millions of people in Africa. More recently, sero-surveillance of healthy blood donors conducted in 2019 revealed high rates of unreported ONNV infection in Uganda. Due to similar clinical symptoms with other endemic mosquito-borne pathogens in the region, including chikungunya virus, dengue virus and malaria, ONNV infections are often un- or misdiagnosed. Elucidating the immunopathogenic factors of this re-emerging arbovirus is critical with the expanding geographic distribution of competent vectors. This study reports the establishment of an immune competent C57BL6/J mouse model to mechanistically characterize ONNV infection and assess potential treatment efficacy. This mouse model successfully recapitulated arthralgia and viremia profiles seen in ONNV patients. Furthermore, longitudinal in-vivo PET imaging with [18F]FB-IL-2 (CD25+CD4+ binding probe) and histopathological assessment in this model demonstrated the pathogenic role of CD4+ T cells in driving joint pathology. Concordantly, in vivo CD4+ T cell depletion, or suppression with fingolimod, an FDA-approved immunomodulating drug, abrogated CD4+ T cell-mediated disease. This study demonstrates the importance of this immune competent ONNV model for future studies on factors influencing disease pathogenesis, which could shape the discovery of novel therapeutic strategies for arthritogenic alphaviruses.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
This study is funded by SIgN, Agency for Science, Technology and Research (A∗STAR) core grant and the Biomedical Research Council, A∗STAR. The flow cytometry platform is part of the SIgN Immunomonitoring platform and supported by a BMRC IAF 311006 grant and BMRC transition funds #H16/99/b0/011.
Description:
This is an open access publication.
ISSN:
1664-3224
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