There are new ways to stop the epidemic of mosquito-borne viruses

Summer is coming, and pesky mosquitoes are on the move. Don't think that the mosquito is just a bag on the body, it flies around to suck blood, and easily brings the virus of the "upper home" to the human body and causes infectious diseases.

On April 19, the team of Professor Cheng Gong of Tsinghua University's School of Basic Medical Sciences and his collaborators published a paper in Science, proposing a new strategy to stop mosquito-borne infectious diseases. They discovered a key environmental symbiotic bacteria in Yunnan Province, which can effectively block mosquitoes from carrying and transmitting the virus by intervening in the environment of this symbiotic bacteria.

Why mosquitoes are susceptible to viruses

Mosquito-borne virus infections are one of the serious threats to human life and health. Among them, dengue fever and Zika fever are the most representative mosquito-borne virus infectious diseases.

Dengue fever is endemic in more than 100 countries around the world. On the mainland, Yunnan is the main area where virulent mosquito-borne viruses such as dengue fever are prevalent. Zika fever has had major outbreaks in the Pacific Islands and South America, with more than 223,000 infections in a year, and thousands of cases of neonatal microcephaly.

"As of now, there are no effective drugs and vaccines for most mosquito-borne virus infectious diseases. People rely on the large-scale use of insecticides to sanitize mosquitoes, which is not only harmful to human health and environmental ecology, but also cannot control the spread of mosquito-borne viruses. This is because mosquitoes can quickly develop resistance and render insecticides ineffective. Cheng Gong, the paper's corresponding author, told China Science Daily that there is an urgent need for low-cost, environmentally-friendly prevention and control strategies to stop the widespread spread of mosquito-borne viruses.

Cheng Gong's team has been paying attention to the regulatory relationship between mosquito gut microbes and mosquito-borne viruses. The transmission route of mosquito-borne viruses is that mosquitoes first suck the blood containing the virus from the infected person, and then the virus infects the mosquito's intestinal cells and spreads to the mosquito's body, and then infects the mosquito's salivary glands, giving the mosquito the ability to transmit the virus.

"Since mosquito intestinal tissue is the first tissue and organ to be invaded, the mosquito gut microbiota must have had a complex interaction with the virus, which determines the susceptibility of mosquitoes to the virus. Cheng Gong said that this has become a consensus in the academic community.

Starting with the intestinal symbiotic bacteria of mosquitoes, researchers have discovered the "accomplice" of the virus, Serratia marcescens, in the population of Aedes aegypti mosquitoes raised in the laboratory. It can assist viruses to infect mosquito intestinal epithelial cells and improve mosquito susceptibility to viruses.

Target bacteria from thousands of mosquitoes in the wild

In the laboratory, are there intestinal commensal bacteria in nature that affect the susceptibility of mosquitoes to viruses? Is it possible to block mosquitoes from carrying and spreading viruses by regulating symbiotic bacteria?

In fact, the natural environment is very different from the laboratory environment. In nature, the composition and abundance of intestinal microorganisms of mosquitoes in the wild are greatly affected by the living environment, some from the environmental microorganisms of breeding waters, and some from the symbiotic microorganisms of environmental plant juice and nectar. The composition of environmental microorganisms varies greatly in different regions, resulting in significant differences in the ability of mosquitoes to carry and transmit viruses.

Therefore, the researchers decided to go deep into the field to conduct research.

In the three years since 2020, researchers have captured thousands of female Aedes mosquitoes in the wild in the border areas of Yunnan. "We isolated and cultivated 55 strains of mosquito intestinal symbiotic bacteria, mixed them with human blood and viruses, and fed them to mosquitoes to see if there were any symbiotic bacteria that could prevent mosquitoes from carrying viruses. Cheng Gong introduced.

Studies have shown that colonization of a bacterium of the genus Rosenberg _YN46 in the guts of Aedes albopictus and Aedes aegypti can significantly inhibit mosquitoes from contracting dengue virus and Zika virus through biting and sucking blood.

Rosenbergella is associated with plant sap and nectar and is widely found in nature. It reshapes the intestinal microenvironment of mosquitoes by secreting a glucose dehydrogenase enzyme that rapidly acidifies the intestinal environment of blood-sucking mosquitoes.

A large number of studies have shown that the envelope proteins of mosquito-borne viruses such as dengue virus are sensitive to acidic signaling. When the virus is in an acidic environment with a pH value of less than 6.5, its envelope proteins undergo irreversible allosterism, causing the virus particles to enter a state of uncapsid and lose their infectious activity.

"Therefore, the acidified intestinal environment can directly inactivate the virus particles that enter the intestine, thereby inhibiting the mosquito's ability to acquire the virus by sucking blood, and greatly reducing the susceptibility of mosquitoes to the virus. Cheng Gong introduced.

Environmental interventions in endemic areas

In order to verify the experimental results, the researchers hoped to further investigate whether the dengue epidemic in Yunnan was related to the distribution and colonization of _YN46 Rosenberg bacteria in nature.

It is understood that under the condition of similar climate and environment and similar mosquito population density, there are significant differences in dengue fever epidemic in different regions of Yunnan, and the hotspot areas are obvious.

"According to epidemiological records in the past 10 years, there have been perennial outbreaks of dengue fever in Xishuangbanna and Lincang, while there are almost no local cases of dengue fever in the neighboring Wenshan and Pu'er. Cheng Gong said.

Therefore, they went deep into these four regions, collected mosquitoes from sites with similar climatic and environmental factors, and tested the colonization of Rosenberg _YN46 bacteria in the gut of mosquitoes in the wild.

The analysis found that _YN46 Rosenberg bacteria had a high colonization rate in the mosquito intestines of Wenshan and Pu'er, two non-dengue endemic areas, while the colonization rate was very low in Xishuangbanna and Lincang.

So, is it possible to carry out environmental intervention in the water bodies of the two endemic areas to naturally colonize the Rosenberg _YN46 into the hatched wild mosquitoes?

"We added _YN46 Rosenberg bacteria to the laboratory water, where we incubated wild Aedes albopictus eggs from Xishuangbanna, and then tested the colonization of the commensal bacteria in the guts of the hatched larvae, pupae and adults. Cheng Gong told reporters.

The results showed that Rosenberg _YN46 bacteria could be efficiently colonized into the intestinal tract of incubated mosquitoes through environmental water intervention. At the same time, mosquitoes hatched in the water environment after the intervention are not susceptible to the virus.

Later, researchers carried out on-site intervention experiments in Mengla County, Xishuangbanna Prefecture. They carry out Rosenberg _YN46 intervention in local breeding water bodies and use the local water environment to hatch native mosquitoes. It was found that the proportion of hatched mosquitoes infected with dengue virus decreased significantly.

Safe and reliable mosquito control strategies

In the process of people's battle against mosquito-borne infectious diseases, safety is an issue that cannot be ignored. The Rosenberg _YN46 in this study is a natural environmental symbiotic bacterium, and its symbiotic relationship with mosquitoes has long been stable in nature.

Therefore, Cheng Gong said that the implementation of the Rosenberg _YN46 bacteria environmental intervention strategy only specifically inhibits mosquito infection and transmission of the virus, and will not make mosquitoes develop drug resistance, nor will it affect the survival adaptability of mosquitoes in nature, which is safe and reliable. "This can be used as a prevention and control strategy with great potential for application to stop the natural spread of mosquito-borne viral infectious diseases. Cheng Gong said.

From the perspective of environmental ecology, this study considers and answers the transmission and epidemic law of mosquito-borne virus infectious diseases, and through the environmental intervention of symbiotic bacteria, it can prevent mosquitoes from carrying and spreading viruses in nature. This will provide a new theoretical system and application ideas for the prevention and control of mosquito-borne infectious diseases. Kang Le, academician of the Chinese Academy of Sciences and researcher of the Institute of Zoology of the Chinese Academy of Sciences, commented.

Gao Fu, academician of the Chinese Academy of Sciences and researcher at the Institute of Microbiology of the Chinese Academy of Sciences, said: "This study has discovered an environmental biological factor that can determine the spread of mosquito-borne viruses, and has built a new technical platform and laid a theoretical foundation for the prevention and control of mosquito-borne virus infectious diseases based on the concept of 'One Health'." (Liu Runan)