The emergence and re-emergence of arboviruses is a global health threat, with >700,000 deaths caused by vector-borne diseases annually (WHO, 2024). It is essential to explore new targets for antiviral development, to aid vector-borne disease control.
Arboviruses are transmitted to humans or animals via the bite of infected vectors. Two such viruses are the Chikungunya (CHIKV) and O'nyong nyong (ONNV) viruses. Many CHIKV outbreaks have globally (CDC 2024), while ONNV is currently restricted to Africa with re-emergence potential (Tong et al., 2024). CHIKV infection is transmitted by the Aedesmosquito species (Souza-Neto et al., 2019) and causes severe arthralgia which can lead to long-lasting chronic polyarthralgia and myalgia symptoms in infected individuals (Madewell, Z. J., 2020). Interestingly, although ONNV is most genetically similar to CHIKV with a sequence identity of 77-85% (Vanlandingham et al., 2006), it is transmitted mainly by the Anopheles mosquito species (Hernandez-Valencia et al., 2023). Expectedly, infections from either virus have many overlapping symptoms. However, joint effusion is characteristic of CHIKV infection while cervical lymphadenopathy was reported only during ONNV infection (Vanlandingham et al., 2005). Thus, despite their genetic similarities, CHIKV and ONNV not only infect different primary vector species but also elicit different immune responses in mammalian hosts.
Although extensive research has been done on CHIKV, few studies compare CHIKV and ONNV, and hence the reasons for differential immune responses to their infection remain unknown. We hypothesise that CHIKV and ONNV interact with a set of specialised host factors which allow them to evade the immune system in their mammalian hosts and respective vectors, resulting in different clinical manifestations to either virus' infection. We aim to dissect both host and viral factors involved in this differential immunopathology using both in vivo and in vitro methods.
Our preliminary investigations identified multiple differentially expressed genes (DEGs) in CHIKV- or ONNV-infected mouse draining lymph node cells. Amongst the notable DEGs, host factor OLFML2A was highly upregulated during ONNV infection. The specific role of OLFML2A during alphavirus infection remains unknown. However, our initial findings indicate that OLFML2A overexpression during CHIKV infection results in increased swelling and inflammation. Building on our observations in this study, I will be exploring the potential roles of OLFML2A in enhancing viral replication, modulating the host’s antiviral response, and enhancing vascular permeability or blocking lymphatic drainage. Studying such host factors could lead us closer to developing immunotherapies which modulate the pathology of CHIKV and ONNV.