New insights into how virus-blocking bacterium operates in mosquitoes
New research published inPLOS Pathogensreveals details of the mechanism by which the bacteriumWolbachiablocks viruses in mosquito cells. Monash Biomedicine Discovery Institute’s (BDI) Dr Jiyoti Verma, a member of Associate Professor Ana Traven's group, worked on this paper in collaboration with Professor Scott O’Neill and Dr Saijo Thomas from the Institute of Vector-Borne Disease.
Wolbachia is known to lower mosquitoes’ ability to transmit viral diseases, such as dengue and West Nile, to humans. Scientists are testing whether deliberately infecting mosquito populations with Wolbachia can lower the spread of viral diseases. However, the precise mechanism by which Wolbachia blocks viruses in mosquitoes is unclear.
Most previous investigations into virus-blocking by Wolbachia have focused on mosquitoes’ response to the bacterium; instead, these researchers studied the effects of Wolbachia on dengue and West Nile viruses themselves. They performed a series of experiments to examine the molecular details of each stage of viral infection in Wolbachia-infected mosquito cells.
The researchers found no evidence that Wolbachia inhibits the earlier stages of virus infection, which include binding to the outside of a cell, followed by entry into the cell. Instead, the results suggest that the bacterium inhibits replication once dengue or West Nile virus is inside a mosquito cell. Reduced replication was associated with rapid degradation of viral RNA, and evidence suggested that a mosquito cellular protein called XRN1, an exoribonuclease, may play a key role in this process.
Further evidence showed that the virus-blocking ability of Wolbachia also depends on the initial dose of the virus and how fast it replicates; slowly replicating viruses like dengue are blocked more efficiently than faster ones, such as West Nile.
Dengue infection is increasing worldwide, with 400 million people infected every year. While further research is required to better understand the molecular details behind virus blocking by Wolbachia, these new findings could help inform efforts to use the bacterium to prevent spread of disease.
According to Dr Thomas, collaboration with DECRA Fellow Dr Verma helped to improve the outcome of the study and led the research team to uncover more information about the fate of viral RNA in these cells.
“Whether it's a fungal or viral pathogen, looking deep into the molecular aspects of their interaction with the host is a key step forward in developing strategies to treat these infections,” Dr Jiyoti Verma said.
This has been adapted from a PLoS Pathogens press release.
Read the full paper in PLoS Pathogens titled Wolbachia-mediated virus blocking in mosquito cells is dependent on XRN1-mediated viral RNA degradation and influenced by viral replication rate.