Host serum iron modulates dengue virus acquisition by mosquitoes

Zhu, Yibin; Tong, Liangqin; Nie, Kaixiao; Wiwatanaratanabutr, Itsanun; Sun, Peng; Li, Qingqing; Yu, Xi; Wu, Pa; Wu, Tianshi David; Chen, Yu; Liu, Qiyong; Bian, Zhong-qi; Wang, Penghua; Cheng, Gong

doi:10.1038/s41564-019-0555-x

Cited by 56 publications

(48 citation statements)

References 70 publications

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“…A recent report indicated that Ae. aegypti mosquitoes feeding on sideropenic mice exhibited a higher prevalence of dengue virus, suggesting that the deficiency of serum iron in the human population may contribute to and facilitate the spread of DENV by mosquitoes [54]. In our study, the dose-dependent phosphorylation of ERK were observed in the insulin treated both cells and midguts of Aedes mosquitoes.…”

Section: Plos Neglected Tropical Diseasessupporting

confidence: 50%

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The Ras/ERK signaling pathway couples antimicrobial peptides to mediate resistance to dengue virus in Aedes mosquitoes

et al. 2020

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Aedes mosquitoes can transmit dengue and several other severe vector-borne viral diseases, thereby influencing millions of people worldwide. Insects primarily control and clear the viral infections via their innate immune systems. Mitogen-Activated Protein Kinases (MAPKs) and antimicrobial peptides (AMPs) are both evolutionarily conserved components of the innate immune systems. In this study, we investigated the role of MAPKs in Aedes mosquitoes following DENV infection by using genetic and pharmacological approaches. We demonstrated that knockdown of ERK, but not of JNK or p38, significantly enhances the viral replication in Aedes mosquito cells. The Ras/ERK signaling is activated in both the cells and midguts of Aedes mosquitoes following DENV infection, and thus plays a role in restricting the viral infection, as both genetic and pharmacological activation of the Ras/ERK pathway significantly decreases the viral titers. In contrast, inhibition of the Ras/ERK pathway enhances DENV infection. In addition, we identified a signaling crosstalk between the Ras/ERK pathway and DENV-induced AMPs in which defensin C participates in restricting DENV infection in Aedes mosquitoes. Our results reveal that the Ras/ERK signaling pathway couples AMPs to mediate the resistance of Aedes mosquitoes to DENV infection, which provides a new insight into understanding the crosstalk between MAPKs and AMPs in the innate immunity of mosquito vectors during the viral infection.

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Section: Plos Neglected Tropical Diseasessupporting

confidence: 50%

“…Host blood-derived factors or their metabolites may affect the susceptibility of mosquitoes to parasites and arboviruses infection [47,54]. Previous studies reveals that infection with malaria parasites can increase blood insulin levels by over10-fold than that of a healthy adult [55].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

The Ras/ERK signaling pathway couples antimicrobial peptides to mediate resistance to dengue virus in Aedes mosquitoes

et al. 2020

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“…At late stages of infection there was depletion of the autophagic inducing JNK and MAPK cascades in addition to repression of JAK/STAT signaling pathways through repression of NF-kB and MAPK signaling, both of which have positive impacts on alphaviral replication [35 – 36]. There was also upregulation of iron binding proteins which might suggest host sequestration of iron in response to viral infection [37 – 38], as well as an upregulation of lipases which should lead to the production of lipid droplets which accumulate in immune challenged cells and aid in the recruitment of signaling molecules following Toll-like receptor activation [39].…”

Section: Resultsmentioning

confidence: 99%

Mayaro Virus Infection Elicits an Innate Immune Response inAnopheles stephensi

Henderson

Brustolin

Hegde

et al. 2020

Preprint

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Mayaro virus (MAYV) is an arboviral pathogen in the genus Alphavirus that is circulating in South America with potential to spread to naïve regions. MAYV is also one of the few viruses with the ability to be transmitted by mosquitoes in the genus Anopheles, as well as the typical arboviral transmitting mosquitoes in the genera Aedes and Haemagogus. Few studies have investigated the infection response of Anopheles mosquitoes. In this study we detail the transcriptomic and small RNA responses of An. stephensi to infection with MAYV via infectious bloodmeal at 2, 7, and 14 days post infection (dpi). 361 unique transcripts were significantly regulated and 79 novel miRNAs were identified. Gene ontology analysis of transcripts regulated at each timepoint suggested activation of the Toll pathway at 2 and 7 dpi and repression of pathways related to autophagy at 14 dpi. These findings provide a basic understanding of the infection response of An. stephensi to MAYV and help to identify host factors which might be useful to target to inhibit viral replication in Anopheles mosquitoes.AUTHOR SUMMARYMayaro virus (MAYV) is a mosquito-borne Alphavirus responsible for outbreaks in South America and the Caribbean. In this study we infected Anopheles stephensi with MAYV and sequenced mRNA and small RNA to understand how MAYV infection impacts gene transcription and the expression of small RNAs in the mosquito vector. Genes involved with innate immunity and autophagy are regulated in response to MAYV infection of An. stephensi. We also discovered novel miRNAs and described their expression patterns following bloodmeal ingestion. These results suggest that MAYV does induce a molecular response to infection in its mosquito vector species and that MAYV may have mechanisms to evade the vector immune response.

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“…Also, serum ion can be utilized by the Ae. aegypti iron metabolism pathway to strengthen reactive oxygen species activity in the gut epithelium in order to oppose DENV infection (37). In addition, expression of the redox-sensing gene nuclear factor erythroid-derived factor 2 (Nrf2) limits ZIKV infection by maintaining midgut homeostasis through modulation of reactive oxygen species in the midgut as well as microbiota growth and stem cell proliferation (38).…”

Section: Flavivirus Interaction With Mosquito Immune and Metabolic Ormentioning

confidence: 99%

Flavivirus Infection and Regulation of Host Immune and Tissue Homeostasis in Insects

Harsh

Eleftherianos

2020

Front. Immunol.

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Host serum iron modulates dengue virus acquisition by mosquitoes

Cited by 56 publications

References 70 publications

The Ras/ERK signaling pathway couples antimicrobial peptides to mediate resistance to dengue virus in Aedes mosquitoes

The Ras/ERK signaling pathway couples antimicrobial peptides to mediate resistance to dengue virus in Aedes mosquitoes

Mayaro Virus Infection Elicits an Innate Immune Response inAnopheles stephensi

Flavivirus Infection and Regulation of Host Immune and Tissue Homeostasis in Insects

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