Avaliação da atividade antiviral da proteína Loqs2 em Aedes aegypti frente a arbovírus sob condições representativas de populações naturais brasileiras

Abstract

Arboviruses represent a growing public health challenge in Brazil, particularly due to the simultaneous and recurrent circulation of viruses such as dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV). Given the limitations of traditional vector control strategies, innovative approaches have focused on the genetic modification of Aedes aegypti, requiring a deeper understanding of its antiviral immune mechanisms. The protein Loqs2, exclusive to the Aedes genus and naturally absent in the midgut, was identified as a potential component of the antiviral response. Previous studies from our group demonstrated that ectopic expression of Loqs2 in the midgut of transgenic mosquitoes significantly reduced DENV replication and dissemination, suggesting that Loqs2 functions as a key antiviral regulator in this tissue. However, those findings were limited to DENV and laboratory strains. In this thesis, we evaluated the antiviral activity of Loqs2 against three arboviruses: ZIKV, CHIKV, and Mayaro virus (MAYV). The results revealed a specific antiviral effect against ZIKV, with no significant impact on the Alphaviruses tested. To assess its applicability under field-like conditions, we tested Loqs2 efficacy in mosquitoes with a genetic background representative of Brazilian natural populations. Unlike the Bangkok laboratory strain, field-derived mosquitoes did not exhibit an antiviral response to ZIKV, which may be due to genetic variability or the presence of insect-specific viruses (ISVs). Small RNA sequencing identified natural infection with Phasi Charoen-like virus (PCLV) in the field populations. However, elimination of this ISV from derived lines did not restore Loqs2-mediated antiviral activity, indicating that intrinsic genetic factors may modulate the immune response. Additionally, we observed a significant reduction in the expression of Argonaute-2 (AGO2) in the carcasses of Loqs2-expressing mosquitoes, suggesting that Loqs2’s interaction with the RNA interference (RNAi) pathway may vary depending on the genetic and viromic context. Collectively, these findings highlight the importance of validating genetically based vector control strategies in natural mosquito populations. Such approaches will only be effective and sustainable if they are tested under ecological conditions that reflect the biological reality of vectors in endemic regions.