Wolbachia-mediated virus blocking in mosquito cells is dependent on XRN1-mediated viral RNA degradation and influenced by viral replication rate

Author summary Dengue virus (DENV) is a human pathogen transmitted by Aedes mosquitoes. Infection with DENV causes dengue fever and may develop into life-threatening dengue hemorrhagic fever. Dengue disease is increasing globally and current control methods are proving ineffective in curtailing this growing problem. A novel strategy to stop DENV transmission is currently being trialled in five countries through the introduction of Wolbachia, an insect endosymbiont, into wild Aedes aegypti populations. Various mechanisms have been proposed to explain Wolbachia-mediated virus blocking (WMVB) including the response of the host to Wolbachia and factors like cholesterol, immune genes and miRNAs. Here we followed the fate of virus in mosquito cell lines and found that Wolbachia does not alter virus binding or internalisation. Further tracking of the virus shows that its replication is reduced in the presence of Wolbachia. The reduced replication is associated with increased viral RNA degradation for both DENV and West Nile virus (WNV). Unlike earlier reports, we didn’t find any evidence for miRNA involvement in WMVB. Analysing the viral RNA further shows that the 3’ region of viral RNA is not fully degraded, indicating that the degradation is likely due to the cellular enzyme XRN1. Accumulation of DENV 3’ regions inhibited XRN1 in the absence of Wolbachia and reduced the activity of XRN1 but not in the presence Wolbachia. Knockdown of XRN1 using siRNA resulted in decreased WMVB associated with increased DENV RNA. The magnitude of WMVB is also dependent on the infectious virus dose and the intrinsic rate at which the virus strain replicates. Similar results were seen for different DENV serotypes confirming that slowly replicating viruses are blocked more efficiently by Wolbachia.See it on Scoop.it, via Viruses, Immunology & Bioinformatics from Virology.uvic.ca
Wolbachia-mediated virus blocking in mosquito cells is dependent on XRN1-mediated viral RNA degradation and influenced by viral replication rate
Source: Viral Bioinformatics