Guiding in, chaperoning out
Guiding in, chaperoning out
Due to climate change, globalization, and urbanization, Aedes mosquitoes are spreading to new areas, including parts of Europe. As a result, mosquito-borne viruses such as chikungunya virus (CHIKV) pose a growing threat to public health. Up to one million people are infected worldwide each year, and this number is expected to rise as the habitat of Aedes mosquitoes expands.
In addition to acute symptoms, CHIKV causes long-lasting joint pain in about 40% of symptomatic patients, leading to major medical and socioeconomic consequences. Although vaccines exist, there remains an urgent need for antiviral therapies for those not vaccinated or those who cannot be vaccinated. Viruses replicate only by entering host cells and hijacking their systems to produce new virus particles. This study of Marleen van der Laan focused on identifying host factors essential for CHIKV infection, with the aim of revealing new therapeutic targets. Two proteins, H2-D1 and Lemd3, were identified alongside the known receptor Mxra8 as entry factors. Reduced expression of these proteins markedly decreased CHIKV infection, suggesting their therapeutic potential. The role of Hsp70 chaperones, proteins that support the folding and function of newly synthesized proteins, was also investigated. Reduction of HspA5 and co-chaperones Sil1 and HspH2 significantly lowered production of structural viral proteins and viral particles. Pharmacological inhibition of Hsp70s produced similar effects, not only in cell models but also in mouse skin tissue and living mice, underscoring the promise of this approach.
Together, these results provide new insights into the CHIKV infection cycle and identify novel targets for developing antiviral strategies.