The RNAi Pathway Is Important to Control Mayaro Virus Infection in Aedes aegypti but not for Wolbachia-Mediated Protection

Abstract

Mayaro virus (MAYV), a sylvatic arbovirus belonging to the Togaviridae family and Alphavirus genus, is responsible for an increasing number of outbreaks in several countries of Central and South America. Despite Haemagogus janthinomys being identified as the main vector of MAYV, laboratory studies have already demonstrated the competence of Aedes aegypti to transmit MAYV. It has also been demonstrated that the Wolbachia wMel strain is able to impair the replication and transmission of MAYV in Ae. aegypti. In Ae. aegypti, the small interfering RNA (siRNA) pathway is an important antiviral mechanism; however, it remains unclear whether siRNA pathway acts against MAYV infection in Ae. aegypti. 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 Wolbachia-free Ae. aegypti. On the other hand, we found that Wolbachia-induced resistance to MAYV in Ae. aegypti is independent of the siRNA pathway. Our study brought new information regarding the mechanism of viral protection, as well as on Wolbachia mediated interference.

The Aedes aegypti siRNA pathway mediates broad-spectrum defense against human pathogenic viruses and modulates antibacterial and antifungal defenses

“…Most likely, overexpression of siRNA pathway factors in the midgut tissue alone is not sufficient to completely suppress virus infection, and a few viral particles that will succeed in escaping this tissue are still able to cause systemic infection. Overexpression of multiple siRNA pathway factors, including AGO2 that has shown restriction of Mayaro virus [ 73 ], in multiple tissues could potentially result in a level of refractoriness that would have an epidemiologically significant impact on disease prevalence if WT mosquitoes would be replaced with transgenic. Furthermore, simultaneous transgenic expression of multiple orthogonal antiviral factors is likely to further potentiate virus blocking.…”

Antiviral RNAi Response against the Insect-Specific Agua Salud Alphavirus

“…2 ) cells, highlighting the antiviral role of the exo-siRNA pathway against ASALV. Similarly, silencing or knockout of Ago2 or Dcr2 induced an increase in infection by the tested arthropod-borne alphaviruses ( 15 , 17 , 19 , 38 , 39 ). Furthermore, similar results have been found for arboviruses belonging to other virus families or orders ( 8 ), except for Zika virus (ZIKV), where no antiviral activity was reported for Ago2 in silenced cells ( 9 , 19 ).…”

Antiviral RNAi response against the insect-specific Agua Salud alphavirus

“…ASALV replication is increased in both Ago2 silenced (Figure 5B, Table S2) and Ago2 or Dcr2 knock-out cells (Figure 2); highlighting the antiviral role of the exo-siRNA pathway against ASALV. Similarly, silencing or knock-out of Ago2 or Dcr2 induced an increase in infection of tested arthropod-borne alphaviruses (Campbell et al, 2008; Schnettler et al, 2013; Sucupira et al, 2020; Varjak, Dietrich, et al, 2018; Varjak, Donald, et al, 2017). Furthermore, similar results have been found for arboviruses belonging to other virus families or orders (Liu et al, 2019), except for ZIKV, where no antiviral activity was reported for Ago2 (Scherer et al, 2021; Varjak, Donald, et al, 2017).…”