By Jean Balchin 05/03/2018

A recent study published in PLOS Pathogens has revealed more details of the mechanism by which the bacterium Wolbachia blocks viruses in mosquito cells. Professor Scott O’Neill, Director of the World Mosquito Program, led by Australia’s Monash University, and colleagues argue that the mechanism reduces viral replication inside cells and that rapid degradation of viral RNA is involved. 

What is Wolbachia? 

Wolbachia is a genus of gram-negative bacteria, a group of bacteria characterised by their cell envelopes, which are composed of a thin peptidoglycan cell ball squished between an inner cytoplasmic cell membrane and a bacterial outer membrane. If you’ve ever studied biology at undergrad, you may remember that gram-negative bacteria do not retain the crystal violet stain used in the gram-staining method of bacterial differentiation.

Wolbachia infects arthropod species, and is one of the world’s most common parasitic microbes. It has been estimated that Wolbachia is possibly the most common reproductive parasite in the biosphere, with complex interactions with its various hosts. In some cases, the relationship between host and Wolbachia is mutualistic rather than parasitic.

It was previously discovered that Wolbachia can lower a mosquitoes’ ability to transmit viral diseases, such as dengue, chikungunya and Zika, to humans. Scientists are testing whether deliberately infecting mosquito populations with Wolbachia can stop the spread of these diseases. However, the precise mechanism by which Wolbachia blocks viruses in mosquitoes is unclear.

While most investigations into Wolbachia’s virus blocking mechanism have focused on mosquitoes’ response to the bacterium, O’Neill and colleagues studied the effects of Wolbachia on dengue and West Nile viruses themselves, performing a series of experiments to examine the molecular details of each stage of viral infection in Wolbachia-infected mosquito cells.

Wolbachia does not affect DENV binding or internalisation but viral RNA replication.

No evidence was found to suggest that Wolbachia inhibits the earlier stages of virus infection, in which the virus binds to the outside of the cell, and then inserts itself inside. Rather, the researchers found evidence that would suggest the bacterium inhibits replication once the dengue or West Nile virus has infiltrated a mosquito cell. This reduced replication was associated with the rapid degeneration of viral DNA. Evidence suggested that a mosquito cellular protein called XRN1 may play a key role in this process.

O’Neill and colleagues also found evidence to indicate that the virus-blocking ability of Wolbachia also depends on the initial dose of the virus and how fast it replicates. In short, slowly replicating viruses such as dengue are blocked more effectively than faster ones, like the West Nile virus.

What is Dengue fever?

Dengue fever is a mosquito-borne tropical disease caused by the dengue virus, wherein people suffer from a high fever, headache, vomiting, muscle and joint pains, and a characteristic skin rash. Symptoms typically develop between three and fourteen days after infection, and recovery usually takes two to seven days. In a few cases, the disease can develop into dengue hemorrhagic fever, resulting in blood plasma leakage, bleeding, low levels of blood platelets. In some cases, it can also develop into dengue shock syndrome, in which dangerously low blood pressure occurs. Dengue infection is increasing globally, with around 400 million people infected each year. Although further research is needed to learn more about the molecular details behind virus blocking by Wolbachia, these new findings could help inform efforts to use the bacterium to prevent spread of disease.

“We now have a better understanding of the mechanism by which Wolbachia inhibits replication of the dengue virus and leads to the degradation of viral RNA in the mosquito cell,” O’Neill explains. “This is an important step forward in deepening our understanding of the mechanistic basis of our approach to tackling the increasing global arbovirus burden.”

Image: Wolbachia is associated with reduced replication of dengue, West Nile viruses and breakdown of their RNA