Chan, Yi-Hao, Teo, Teck-Hui, Torres-Ruesta, Anthony, Hartimath, Siddesh V, Chee, Rhonda Sin-Ling, Khanapur, Shivashankar, Yong, Fui Fong, Ramasamy, Boominathan, Cheng, Peter, Rajarethinam, Ravisankar et al (show 6 more authors)
(2020)
Longitudinal [18F]FB-IL-2 PET Imaging to Assess the Immunopathogenicity of O'nyong-nyong Virus Infection.
FRONTIERS IN IMMUNOLOGY, 11.
894-.
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 <i>in-vivo</i> PET imaging with [<sup>18</sup>F]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, <i>in vivo</i> 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.
Item Type: | Article |
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Uncontrolled Keywords: | O'nyong-nyong virus, alphavirus, immunopathogenesis, CD4+T cells, drug repositioning, PET imaging |
Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
Depositing User: | Symplectic Admin |
Date Deposited: | 28 May 2021 09:23 |
Last Modified: | 18 Jan 2023 22:37 |
DOI: | 10.3389/fimmu.2020.00894 |
Open Access URL: | http://doi.org/10.3389/fimmu.2020.00894 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3124344 |