| Summary: | Mayaro virus (MAYV), a sylvatic arbovirus belonging to the <i>Togaviridae</i> family and <i>Alphavirus</i> genus, is responsible for an increasing number of outbreaks in several countries of Central and South America. Despite <i>Haemagogus janthinomys</i> being identified as the main vector of MAYV, laboratory studies have already demonstrated the competence of <i>Aedes aegypti</i> to transmit MAYV. It has also been demonstrated that the <i>Wolbachia</i><i>w</i>Mel strain is able to impair the replication and transmission of MAYV in <i>Ae. aegypti</i>. In <i>Ae. aegypti</i>, the small interfering RNA (siRNA) pathway is an important antiviral mechanism; however, it remains unclear whether siRNA pathway acts against MAYV infection in <i>Ae. aegypti</i>. The main objective of this study was to determine the contribution of the siRNA pathway in the control of MAYV infection. Thus, we silenced the expression of AGO2, an essential component of the siRNA pathway, by injecting dsRNA-targeting AGO2 (dsAGO2). Our results showed that AGO2 is required to control MAYV replication upon oral infection in <i>Wolbachia</i>-free <i>Ae. aegypti</i>. On the other hand, we found that <i>Wolbachia</i>-induced resistance to MAYV in <i>Ae. aegypti</i> is independent of the siRNA pathway. Our study brought new information regarding the mechanism of viral protection, as well as on <i>Wolbachia</i> mediated interference.
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