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2024

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09

Hainan Medical University Xia Ganfeng Collaboration Shows Intestinal Symbiont-Derived Sphingosine Regulates Aedes Vector Capacity

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The main vectors of Zika virus (ZIKV) and dengue virus (DENV) are Aedes aegypti and Aedes albopictus, Aedes aegypti is more capable of transmission. However, the underlying mechanism remains unclear.

On September 19, 2024, Zou Zhen, Zheng Aihua of the Chinese Academy of Sciences and Xia Ganfeng of Hainan Medical University jointly communicated inNature CommunicationsOnline is titled“Gut symbiont-derived sphingosine modulates vector competence inAedesmosquitoes”The research paper,The studyThe findings highlight the potential of intestinal commensal bacteria (such as Eh_B17) to modulate the ability of Aedes arbovirus vectors. As a natural antiviral drug, Eh_B17 is expected to be a potential candidate for blocking the spread of ZIKV/DENV.

Aedes albopictus was found to have a vector capacity comparable to ZIKV/DENV with Aedes aegypti, either by blood feeding or intrathoracic injection after antibiotic treatment. This suggests that the midgut microbiota can influence vector capacity. Enterobacter howii b17 (Eh_B17) was isolated from Enterobacter aegypti collected in the field and developed resistance to ZIKV/DENV infection after intestinal transplantation in Aedes aegypti. Sphingosine, a metabolite secreted by Eh_B17, potently inhibits ZIKV infection by blocking viral entry in Aedes aegypti and cell culture with an IC50 of about 10 μM.Field survey results showed that Eh_B17 was more likely to colonize Aedes albopictus, and Aedes albopictus was more resistant to Zika virus infection.

Aedes mosquitoes are the main vectors of highly pathogenic arboviruses,Such as Zika virus (ZIKV), dengue virus (DENV) and chikungunya virus (CHIKV), pose a threat to public health. C is widely distributed in the world, especially in tropical and subtropical environments, and is closely related to urban areas. Aedes albopictus is highly adaptable to new environments. It has expanded its distribution to temperate regions and has become an increasingly important vector of disease transmission. This expansion of scope provides new opportunities for viruses to cause epidemics. Studies have shown that,Although both Aedes aegypti and Aedes albopictus viruses can transmit Zika virus and dengue virus, Aedes albopictus virus is a minor vector of Zika virus and dengue virus compared to Aedes aegypti virus.

ZIKV, closely related to DENV, is a single-strand positive RNA flavivirus.Many clinical symptoms are caused by Zika virus, which range from asymptomatic or mild symptoms to severe neurological complications.Flaviviruses are mainly transmitted to humans by mosquitoes. After the mosquito acquires the virus by feeding on the blood of an infected host, the virus replicates and spreads through the midgut epithelium and spreads from the blood system to other tissues, including fat bodies, the nervous system, and salivary glands. Infected mosquitoes can bite and spread the virus to other hosts.Therefore, the midgut, blood glands and salivary glands of mosquitoes are important organs for virus replication or transmission.

The midgut is the site of multi-taxa interaction in the host.These include commensal microorganisms and pathogens, which ultimately affect pathogen infection. The intestinal commensal bacterium Chromobacter reduces the susceptibility of mosquitoes to Plasmodium falciparum and dengue virus by producing stable bioactive factors. Aedes aegypti promotes DENV infection by inhibiting trypsin transcription and enzyme catalysis. These results suggest that gut microbes can play a key role in the regulation of infection by microbial and viral pathogens.Symbionts can affect the host's metabolism and physiology, such as lipid metabolism. Sphingolipids (SLs) can act as receptors for toxins, viruses and bacteria. SLs are common in eukaryotes, but only a few bacteria can produce them, such as species of the phyla Bacteroides and Chlorophyta.Previous studies have suggested that bioactive lipids produced by the gut microbiota may cross the epithelial barrier and interact with host metabolism.

Sphingosine (Sph) is the key molecule of SLs, which is the main membrane component of many complex biological processes such as cell growth, differentiation, development, autophagy and apoptosis.Sph has strong antibacterial activity against a variety of pathogenic bacteria, and more studies on the antibacterial activity of Staphylococcus aureus and Pseudomonas aeruginosa. However, the direct effect of sphingosine on the virus has only recently been studied. Endogenous sphingosine prevents herpes simplex virus type 1 (HSV-1) infection by limiting fusion of viral endosomes through the formation of intraluminal vesicles. In addition, sphingosine blocked the infection of human epithelial cells by SARS-CoV-2 pseudovirion particles by binding to the SARS-CoV-2 cell receptor ACE2.However, it is unclear whether sphingosine can inhibit flavivirus infection.

Studies have shown that the midgut microbiota of Aedes mosquitoes modulate their vector capacity.Eh_B17 was isolated from Aedes albopictus collected in the field and found to produce sphingosine, a metabolite that inhibits ZIKV infection (C6/36 and Vero cells) by limiting viral fusion with membranes. The results showed that Eh_B17 was more inclined to colonize Aedes albopictus than Aedes aegypti.These results suggest that symbiotic colonization of sphingosine-producing bacteria can affect the vector capacity of Aedes mosquitoes and is potentially important in mosquito-borne disease control strategies.

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