Interplay between autophagy and Sindbis virus in cells derived from key arbovirus vectors, Aedes albopictus and Aedes aegypti mosquitoes.

Aedes albopictus and Aedes aegypti are two species of Aedes mosquitoes which transmit multiple arboviruses causing serious diseases in human. Intriguingly, infection of arbovirus in both Aedes mosquitoes does not cause dramatic pathology, indicating that both mosquitoes have evolved mechanisms to tolerate persistent infection and restrict viral replication to nonpathogenic levels. Therefore, understanding how these mosquitoes interact with viruses would help to find targets for controlling the related mosquito-borne diseases. Autophagy is a conserved cellular recycling process functioning in maintenance of cellular homeostasis and recirculation of cytoplasmic materials under stressful conditions. Autophagy also acts as a cellular defense mechanism against viral infection. It is known that autophagy plays important roles in the replication of several Aedes mosquito-borne viruses in mammalian systems. However, little information is available regarding the role of autophagy in replication of those viruses in their primary vector, Aedes mosquitoes. This study found that interaction between autophagy and replication of Sindbis virus (SINV) occurred in Aedes albopictus C6/36 cells and Ae. aegypti Aag2 cells. Moreover, it discovered that the patterns of interaction between autophagy and SINV replication are different in C6/36 cells and Aag2 cells. It was shown that replication of SINV induced complete autophagy in C6/36 cells but suppressed autophagy in Aag2 cells. Moreover, induction of autophagy by rapamycin treatment restricted SINV replication in C6/36 cells but promoted SINV replication in Aag2 cells. Consistent with this, suppression of autophagy by down regulation of Atg8 promoted SINV replication in C6/36 cells but restricted SINV replication in Aag2 cells. It was also found that, in both C6/36 and Aag2 cells, interaction between autophagy and SINV replication occurred after viral entry and prior to viral assembly. Collectively, this work demonstrated that SINV replication manipulated autophagy in Aedes mosquito cells and provided strong evidence of the role autophagy played in viral replication in Aedes mosquitoes. The findings have laid a foundation to elucidate the correlation between autophagy and arbovirus replication in Aedes mosquitoes and could help to understand the difference in viral transmission capacity of the two Aedes mosquitoes, Ae. albopictus and Ae. aegypti.