Mosquito antiviral defense mechanisms: a delicate balance between innate immunity and persistent viral infection

Lee, Wai-Suet; Webster, Julie A.; Madzokere, Eugene T.; Stephenson, Eloise; Herrero, Lara J.

doi:10.1186/s13071-019-3433-8

Cited by 86 publications

(88 citation statements)

References 118 publications

(182 reference statements)

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“…More specifically, the activation of the dual oxidase (DUOX) pathway in Drosophila following infection with the enteric pathogen, Erwinia carotovora subspecies carotovora, has been shown previously [53]. In the case of mosquitoes, gut immunity has been explored to a reasonable level in regard to viral infection [54,55]. This study advances this understanding by relating gut immunity to the autophagy marker protein Atg8 and describing one method by which mosquitoes respond to bacterial and fungal infections.…”

Section: Discussionmentioning

confidence: 95%

Aedes albopictus Autophagy-Related Gene 8 (AaAtg8) Is Required to Confer Anti-Bacterial Gut Immunity

Kim

Park

et al. 2020

IJMS

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Autophagy is an important process by which pathogens and damaged or unused organelles are eliminated. The role of autophagy in development and the immune response to pathogens is well established. Autophagy-related protein 8 (Atg8) is involved in the formation of the autophagosome and, with the help of the serine protease Atg4, mediates the delivery of both vesicles and the autophagosome to the vacuole. Here, we cloned the Aedes albopictus autophagy-related protein 8 (AaAtg8) gene and characterized its role in the innate immunity of the mosquito against microbial infections. AaAtg8 is comprised of an open reading frame (ORF) region of 357 bp encoding a polypeptide of 118 amino acid residues. A domain analysis of AaAtg8 revealed an Atg8 ubiquitin-like domain, Atg7/Atg4 interaction sites, and peptide binding sites. The AaAtg8 mRNA expression was high in the Malpighian tubules and heads of both sugar-fed and blood-fed adult female mosquitoes. The expression level of AaAtg8 mRNA increased in the midgut and abdominal carcass following being challenged with Listeria monocytogenes. To investigate the role of AaAtg8 in the innate immune responses of Ae. albopictus, AaAtg8 gene-silenced adult mosquitoes were challenged by injection or by being fed microorganisms in blood. High mortality rates were observed in mosquitoes in which AaAtg8 was silenced after challenges of microorganisms to the host by blood feeding. This suggests that Atg8-autophagy plays a critical role in the gut immunity in Ae. albopictus.

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Section: Discussionmentioning

confidence: 95%

Aedes albopictus Autophagy-Related Gene 8 (AaAtg8) Is Required to Confer Anti-Bacterial Gut Immunity

Kim

Park

et al. 2020

IJMS

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“…Viral infection triggers the activation of innate immunity pathways and leads to the transcription of genes responsible for antiviral responses in mosquitoes [60][61][62]. Innate immunity is a functional response against foreign organisms, formed in the long-term evolution process of mosquitoes after frequent viral infection, including RNA interference pathways, JAK-STAT, Toll and Imd pathways [63,64]. We will further focus on studying the relationship between mosquitoes' innate immune system or immune-related genetic loci and vector competence.…”

Section: Discussionmentioning

confidence: 99%

Genetic structure and vector competence for DENV-2 of Aedes albopictus (Diptera: Culicidae) populations in China

Wang

Deng

et al. 2020

Preprint

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Background: As a vector of over 20 arboviruses, Aedes albopictus has spread throughout the world mostly since the second half of the twentieth century, and it is now found on every continent except Antarctica. Approximately 50-100 million people are infected with dengue virus (DENV) transmitted by Aedes mosquitoes each year, leading to a heavy economic burden on both governments and individuals. Understanding the population genetics and vector competence of vector species is critical to effectively preventing and controlling vector-borne diseases. The aim of this study was to examine the genetic structure and vector competence for dengue virus type 2 (DENV-2) of Ae. albopictus populations across China and their relationship.Methods: From July to September in 2019, Ae. albopictus eggs were collected by using ovitraps in 8 localities across China and reared to adults in laboratory. The mitochondrial gene cytochrome c oxidase subunit 1 (cox1) were used to examine the patterns of genetic diversity and population structure among native Ae. albopictus populations. The vector competence was detected by quantitative analysis of DENV-2 virus titer in mosquito tissues (midguts, heads and salivary glands) through qRT-PCR. The correlation between population genetic indices and DENV-2 loads in the mosquitoes’ tissues was also examined.Results: A total of 20 haplotypes of mtDNA cytochrome c oxidase subunit 1 (cox1) were identified in the 120 specimens from the eight tested populations. The dominate haplotype H01 was detected in seven geographic populations of mainland China. Genetic parameters such as haplotype diversity (Hd), nucleotide diversity (π), and fixation index (FST) revealed the population diversity decreasing from south to north, and low population genetic differentiation. STRUCTURE analysis indicated that Ae. albopictus populations in southern China were clustered. In addition, The Mantel test indicated a positive correlation between genetic distance and geographical distance (R2 = 0.364, P = 0.003). We observed no correlation between population genetic indices of cox1 in Ae. albopictus populations and DENV-2 virus loads. However, the southern populations had the low DENV-2 virus loads generally.Conclusion: Conventional genetic markers such as cox1 may not reflect genetic differences in mosquitoes’ vector competence in different regions. The fact of lower DENV-2 loads in southern populations may be associated with the stable immunity system established in mosquitoes due to the long-term prevalence of dengue disease in these areas. The genetic structure and vector competence of Ae. albopictus populations in this study may have implications for understanding the epidemiology, prevention and control of vector-borne diseases.

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“…Some of these miRNAs have been proposed to be used as biomarkers in dengue-infected patients [189,190]. Interestingly, modulation of microRNA expressions have been also described upon DENV infection of insect cells (e.g., C6/36 cells) as well as adult vector mosquitoes such as Aedes albopictus [191][192][193], suggesting that DENV might also regulate the activation of these antiviral RNAi pathways in vector mosquitoes, potentially avoiding viral clearance that promotes viral replication and transmission [194]. Despite RNAi constituting an evolutionarily conserved phenomenon of the mosquito-innate immune response to virus infections [195], viruses have found ways to subvert the RNAi-mediated antiviral responses in vector mosquitoes to manipulate miRNA profiles to their own benefit [196].…”

Section: Denv Infection and The Host Innate Immune Responsesmentioning

confidence: 99%

Dengue Immunopathogenesis: A Crosstalk between Host and Viral Factors Leading to Disease: Part I - Dengue Virus Tropism, Host Innate Immune Responses, and Subversion of Antiviral Responses

Puerta-Guardo¹,

Biering²,

Harris³

et al. 2020

Dengue Fever in a One Health Perspective

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Dengue is the most prevalent emerging mosquito-borne viral disease, affecting more than 40% of the human population worldwide. Many symptomatic dengue virus (DENV) infections result in a relatively benign disease course known as dengue fever (DF). However, a small proportion of patients develop severe clinical manifestations, englobed in two main categories known as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Secondary infection with any of the four dengue virus serotypes (DENV1, -2, -3, and -4) is a risk factor to develop severe forms of dengue disease. DSS is primarily characterized by sudden and abrupt endothelial dysfunction, resulting in vascular leak and organ impairment, which may progress to hypovolemic shock and death. Severe DENV disease (DHF/DSS) is thought to follow a complex relationship between distinct immunopathogenic processes involving host and viral factors, such as the serotype cross-reactive antibody-dependent enhancement (ADE), the activation of T cells and complement pathways, the phenomenon of the cytokine storm, and the newly described viral toxin activity of the nonstructural protein 1 (NS1), which together play critical roles in inducing vascular leak and virus pathogenesis. In this chapter that is divided in two parts, we will outline the recent advances in our understanding of DENV pathogenesis, highlighting key viral-host interactions and discussing how these interactions may contribute to DENV immunopathology and the development of vascular leak, a hallmark of severe dengue. Part I will address the general features of the DENV complex, including the virus structure and genome, epidemiology, and clinical outcomes, followed by an updated review of the literature describing the host innate immune strategies as well as the viral mechanisms acting against and in favor of the DENV replication cycle and infection.

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Mosquito antiviral defense mechanisms: a delicate balance between innate immunity and persistent viral infection

Cited by 86 publications

References 118 publications

Aedes albopictus Autophagy-Related Gene 8 (AaAtg8) Is Required to Confer Anti-Bacterial Gut Immunity

Aedes albopictus Autophagy-Related Gene 8 (AaAtg8) Is Required to Confer Anti-Bacterial Gut Immunity

Genetic structure and vector competence for DENV-2 of Aedes albopictus (Diptera: Culicidae) populations in China

Dengue Immunopathogenesis: A Crosstalk between Host and Viral Factors Leading to Disease: Part I - Dengue Virus Tropism, Host Innate Immune Responses, and Subversion of Antiviral Responses

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