Wednesday, May 04, 2016

Cell Host & Microbe: Wolbachia Blocks Zika Virus In Brazilian Aedes Aegypti Mosquitoes

Aedes Aegypti - Credit Wikipedia

# 11,340

In 2010  the mosquito-disease control world was abuzz with news of a promising method to prevent mosquitoes from carrying, and passing on, dengue to humans. It involved infecting mosquitoes with Wolbachia, a bacterium commonly carried by a variety of insects around the world, and then releasing them into the wild.

Scientists discovered that when mosquitoes are infected with certain strains of Wolbachia, their lifespan was shortened and their ability to transmit dengue was greatly reduced, although the exact mechanism behind those effects wasn’t understood.

When an infected male mosquito mates with an uninfected female, the resultant fertilized eggs will fail to mature due to an abnormality known as cytoplasmic incompatibility (CI). Only the offspring from the union between already infected parents survive.

Since the Wolbachia infection is passed down from one generation to the next, that is expected to give the Wolbachia infected mosquitoes quite an evolutionary advantage.

We looked at some early trials back in 2011, and preliminary results were impressive.  Scientists in Queensland, Australia began released thousands of Wolbachia infected mosquitoes each week into the remote communities of Gordonvale and Yorkeys Knob, and within weeks infected mosquitoes overran the uninfected mosquito population in both test environments.

Hopes have even been raised that Wolbachia might be used to control malaria as well, as laboratory studies showed that infected anopheles stephensi mosquitoes developed resistance to malarial infection.

But whether Wolbachia would have a similar effect on the carriage and transmission of Zika virus has only been theorized, not proven. Today, researchers at the FIOCRUZ (Fundação Oswaldo Cruz) Institute have published a study in Cell Host & Microbe, where they test the theory using Brazilian Ades Agypti mosquitoes.

The results appear promising, at least in the mosquito species (Aedes Aegypti) tested, with infected mosquitoes dramatically less able to transmit the virus.

First a link and an excerpt from the open access study, then some excerpts from the press release.

Publication stage: In Press Corrected Proof
Open Access


Our results indicate that the ability of Wolbachia infection to greatly reduce the capacity of mosquitoes to harbor and transmit a range of medically important pathogens, including the dengue and chikungunya viruses (Caragata et al., 2016, Moreira et al., 2009, Walker et al., 2011) also extends to ZIKV. While wMel did not completely inhibit ZIKV infection, we observed a similar decrease in prevalence and intensity of infection to that of wMel-infected Ae. aegypti challenged with viremic blood from dengue patients, which was considered sufficient to drastically decrease viral transmission (Ferguson et al., 2015). Additionally, the fact that we did not observe an increase in disseminated ZIKV infection over time, and that ZIKV prevalence and infectivity in wMel_Br mosquito saliva was significantly decreased, may indicate that, as for dengue, wMel extends the ZIKV extrinsic incubation period (Ye et al., 2015). This in turn would likely further decrease overall ZIKV transmission rates, given the small decrease in lifespan associated with wMel infection (Walker et al., 2011). 

Public Release: 
Inheritable bacterium controls Aedes mosquitoes' ability to transmit Zika
Cell Press

Aedes mosquitoes carrying the bacterium Wolbachia--found inside the cells of 60 percent of all insect species--are drastically less able to transmit Zika virus, say researchers at Brazil's Oswaldo Cruz Foundation (FIOCRUZ) in a study published May 4 in Cell Host & Microbe

This is the first report on the effect of Wolbachia bacteria on Zika virus. Originally inserted into Aedes eggs as part of the Eliminate Dengue Program, the bacterium is passed on from mother mosquitoes to offspring, so it is a sustainable control agent. The approach is already being piloted to control Dengue virus transmission and, with the proper resources and approvals, there's infrastructure in place to increase the scale of current trials to also help tackle the Zika epidemic.

Wolbachia bacteria were first identified in 2005 as a way to combat mosquito-borne infections. After four years, researchers were successful in their attempts to isolate the bacterium from fruit flies and get it inside Aedes mosquitoes' eggs, without using any genetic alteration. They expected Wolbachia to shorten mosquitoes' lifespans, but the bacterium provided an added bonus, in that it heavily reduced the Dengue virus replication in the mosquito. The bacterium, it seems, has the same effect on Zika transmission. The same effect was previously seen on Chikungunya virus, also transmitted by Aedes mosquitoes.

"The idea has been to release Aedes mosquitoes with Wolbachia in the field over a period of a few months, so they mate with Aedes mosquitoes without Wolbachia living in the place and, over time, replace the mosquito population," says senior author Luciano Moreira of the Oswaldo Cruz Foundation. He is also actively involved in the Eliminate Dengue Program, a non-profit that is testing the approach in 40 locations around the world. 

"Zika and Dengue belong in the same family of viruses, so with the outbreak in Brazil, the logical idea was to test the mosquitoes carrying Wolbachia by challenging them with Zika virus and see what would happen" he says.

Moreira's team gave Brazilian field mosquitoes and Wolbachia-infected mosquitoes Zika virus by feeding them human blood infected by two recent strains of the virus that is circulating in Brazil. After two weeks, the researchers saw that mosquitoes carrying Wolbachia had fewer viral particles in their bodies and saliva. The tests showed that the virus present in the mosquito saliva was not active--meaning that, after biting, the mosquito would not be able to transmit Zika virus. The reason for this drop in viral reproduction is unknown, but one theory is that because Wolbachia lives inside of the mosquito's cells, if the virus goes inside the cell to replicate, then there is an internal competition for resources. Surprisingly, this drop held true no matter how many Wolbachia the mosquito carried.

"Wolbachia showed to be as effective on Zika as the most important Dengue experiments we did," Moreira says. He cautions that the strategy is not 100 percent effective nor will it eliminate the virus. "We know that there will not be only one solution for Zika--we have to do this alongside different approaches, like vaccines or insecticides, besides the public measures to control Aedes breeding sites."

He is currently discussing the Wolbachia approach with the Brazilian Ministry of Health, hoping to raise the resources and public support to test its effect on Zika in the field.