A mosquito salivary protein promotes flavivirus transmission by activation of autophagy

Sun, Peng; Nie, Kaixiao; Zhu, Yibin; Liu, Yang; Wu, Pa; Liu, Ziwen; Du, Senyan; Fan, Huahao; Chen, Chunhong; Zhang, Renli; Wang, Penghua; Cheng, Gong

doi:10.1038/s41467-019-14115-z

Cited by 102 publications

(107 citation statements)

References 69 publications

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“…The salivary factor LTRIN from Aedes aegypti mosquitoes facilitates the transmission of ZIKV and exacerbates its pathogenicity by interfering with the lymphotoxin-β receptor in mice [23]. The saliva-specific protein AaVA-1 from Aedes aegypti mosquitoes promotes dengue and Zika virus transmission by activating autophagy in host immune cells of the monocyte lineage [24]. According to these previous findings in other flavivirus species, we speculate that the non-identified component(s) from the saliva of JEV-infected Cx.…”

Section: Discussionmentioning

confidence: 99%

Experimental Infection of Newly Hatched Domestic Ducklings via Japanese Encephalitis Virus-Infected Mosquitoes

Zhang

et al. 2020

Pathogens

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Japanese encephalitis virus (JEV) is a zoonotic pathogen that is maintained by mosquito vectors and vertebrate hosts including birds in a natural transmission cycle. Domestic ducklings are sensitive to JEV infection, but the clinical responses of domestic ducklings to natural JEV infection are unknown. In this study, we simulated the natural JEV infection of domestic ducklings via JEV-infected mosquito bites to evaluate the pathogenicity of JEV in domestic ducklings. Specific pathogen-free domestic ducklings were infected at day 2 post-hatching with JEV-infected Culex pipiens mosquito bites and monitored for clinical responses. Among 20 ducklings exposed to JEV-infected mosquitoes, six showed mild and non-characteristic clinical signs starting at two days post-infection, then died suddenly with neurological signs of opisthotonos (a condition of spasm of the back muscles causing the head and limbs to bend backward and the trunk to arch forward) between two and three days post-infection. The mortality of the affected ducklings was 30% (6/20). Multifocal lymphohistiocytic perivascular cuffs and lymphohistiocytic meningitis were macroscopically observed in the affected duckling brains. JEV was detected in the cytoplasm of neuronal cells in the affected duckling brains by immunohistochemical assays and was recovered from the affected duckling brains by viral isolation. These observations indicated that JEV infection via mosquito bites causes mortality associated with viral encephalitis in newly hatched domestic ducklings, thus demonstrating the potential pathogenicity of JEV in domestic ducklings under natural conditions.

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Section: Discussionmentioning

confidence: 99%

Experimental Infection of Newly Hatched Domestic Ducklings via Japanese Encephalitis Virus-Infected Mosquitoes

Zhang

et al. 2020

Pathogens

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“…The CPE assay, qRT-PCR analysis and Western blot analysis methods were used to explored the anti-ZIKV activity in vitro. For the animal experiment, AG6 mice (ifnar1 -/-ifngr1 -/-) is highly susceptible to ZIKV and thus the strain mice for the testing of CR antivirals activity in vivo (20). The survival rate of mice and viral RNA level expression in blood were observed in our study.…”

mentioning

confidence: 62%

Utilizing network pharmacology to explore the underlying mechanism of Cinnamomi Ramulus in Zika Fever induced by Zika Virus

Zhang

Lin

Lai

et al. 2020

Preprint

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Background: Zika fever is a mosquito-borne infection induced by Zika virus (ZIKV),effective drug and vaccine against ZIKV infection is still unavailable. Cinnamomi ramulus (CR) is a traditional Chinese herb with a long history ,can stimulate secretion of sweat and relieve exterior syndrome. The aim of this research was to evaluate the effect of CR against ZIKV and uncover its mechanism of action by network pharmacology.Methods: Cell viability assay, qRT-PCR assay and western blot assays were perfermed to evaluate anti-ZIKV activity in vitro. Survival rate, body weight were observed and viremia was detected in AG6 mice. Drug- target-disease networks, GO enrichment, and KEGG pathway analysis was established to clarify the therapeutic mechanismsits. Results: In this study, we find that CR can alleviate CPE after Zika virus infection. In the premixed administration mode, CR showed superior activity to inhibit viral RNA replication and protein expression in cells. Orally administered CR effectively protected AG6 mice infected with lethal doses of ZIKV, conferring 50% or 20% survival rate at a dosage of 900mg/ml or 450mg/ml, reducing body weight loss, inhibiting viral RNA replication. Beta-sitosterol, DBP, α-Longipinen, (-)-alpha-cedrene, ()-alpha-Longipinene may the main active compound and PTGS2, GABRA1, PTGS1, PTGES and CCR5 may the main targets. 176 biological processes, 16 cell components, 27 molecular functions, and 37 pathways were significantly identified in GO enrichment and pathway analysis. Conclusions: These results reveal that CR treatment of Zika fever is mainly related to PTGS1 and PTGS2 regulated prostaglandin release, metabolism, and inflammation response.

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“…Hence, vector-derived molecules are critical for Leishmania establishment. Similarly, transmission and dissemination of viruses were also enhanced by bites and saliva of mosquitoes (Pingen et al, 2017;Sun et al, 2020), reinforcing the importance of vector-derived factors in modulating the infectivity of vector-borne pathogens.…”

Section: Introductionmentioning

confidence: 83%

Heme Oxygenase-1 Induction by Blood-Feeding Arthropods Controls Skin Inflammation and Promotes Disease Tolerance

et al. 2020

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A mosquito salivary protein promotes flavivirus transmission by activation of autophagy

Cited by 102 publications

References 69 publications

Experimental Infection of Newly Hatched Domestic Ducklings via Japanese Encephalitis Virus-Infected Mosquitoes

Experimental Infection of Newly Hatched Domestic Ducklings via Japanese Encephalitis Virus-Infected Mosquitoes

Utilizing network pharmacology to explore the underlying mechanism of Cinnamomi Ramulus in Zika Fever induced by Zika Virus

Heme Oxygenase-1 Induction by Blood-Feeding Arthropods Controls Skin Inflammation and Promotes Disease Tolerance

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