Insulin Potentiates JAK/STAT Signaling to Broadly Inhibit Flavivirus Replication in Insect Vectors

Publication date: 12 November 2019Source: Cell Reports, Volume 29, Issue 7Author(s): Laura R.H. Ahlers, Chasity E. Trammell, Grace F. Carrell, Sophie Mackinnon, Brandi K. Torrevillas, Clement Y. Chow, Shirley Luckhart, Alan G. GoodmanSummaryThe World Health Organization estimates that more than half of the world’s population is at risk for vector-borne diseases, including arboviruses. Because many arboviruses are mosquito borne, investigation of the insect immune response will help identify targets to reduce the spread of arboviruses. Here, we use a genetic screening approach to identify an insulin-like receptor as a component of the immune response to arboviral infection. We determine that vertebrate insulin reduces West Nile virus (WNV) replication in Drosophila melanogaster as well as WNV, Zika, and dengue virus titers in mosquito cells. Mechanistically, we show that insulin signaling activates the JAK/STAT, but not RNAi, pathway via ERK to control infection in Drosophila cells and Culex mosquitoes through an integrated immune response. Finally, we validate that insulin priming of adult female Culex mosquitoes through a blood meal reduces WNV infection, demonstrating an essential role for insulin signaling in insect antiviral responses to human pathogens.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research

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(Washington State University) A discovery by a Washington State University-led research team has the potential to inhibit the spread of West Nile virus as well as Zika and dengue viruses. The researchers demonstrated that mammalian insulin activated an antiviral immunity pathway in mosquitoes, increasing the insects' ability to suppress the viruses. Since mosquito bites are the most common way humans are infected with West Nile, stopping the virus among the insects would protect human health.
Source: EurekAlert! - Infectious and Emerging Diseases - Category: Infectious Diseases Source Type: news
eng Li Cao Ye Flaviviruses, such as Zika virus (ZIKV), Japanese encephalitis virus (JEV), Dengue virus (DENV), and West Nile virus (WNV), are important arthropod-borne pathogens that present an immense global health problem. Their unpredictable disease severity, unusual clinical features, and severe neurological manifestations underscore an urgent need for antiviral interventions. Furin, a host proprotein convertase, is a key contender in processing flavivirus prM protein to M protein, turning the inert virus to an infectious particle. For this reason, the current study was planned to evaluate the antiviral ac...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research
Abstract Flaviviruses comprise several medically important viruses, including Japanese encephalitis virus, West Nile virus, dengue virus (DENV), yellow fever virus and Zika virus (ZIKV). A large outbreak of DENV and ZIKV occurred recently, leading to many cases of illness and death. However, despite decades of efforts, we have no clinically specific therapeutic drugs against DENV and ZIKV. Previous studies showed that inflammatory responses play a critical role in dengue and Zika pathogenesis. Thus, in this study, we examined a series of novel anti-inflammatory compounds and found that treatment with compound 2d c...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Contributors : Nandan S Gokhale ; Alexa B McIntyre ; Melissa D Mattocks ; Christopher L Holley ; Helen M Lazear ; Christopher E Mason ; Stacy M HornerSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensThe RNA modification N6-methyladenosine (m6A) can modulate mRNA fate and thus affect many biological processes. We analyzed m6A modification across the transcriptome following infection by dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and hepatitis C virus (HCV). We found that infection by these viruses in the Flaviviridae family alters m6A modification of specific cellular...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
lmair Flaviviruses are the most medically relevant group of arboviruses causing a wide range of diseases in humans and are associated with high mortality and morbidity, as such posing a major health concern. Viruses belonging to this family can be endemic (e.g., dengue virus), but can also cause fulminant outbreaks (e.g., West Nile virus, Japanese encephalitis virus and Zika virus). Intense research efforts in the past decades uncovered shared fundamental strategies used by flaviviruses to successfully replicate in their respective hosts. However, the distinct features contributing to the specific host and tissue tropi...
Source: Viruses - Category: Virology Authors: Tags: Review Source Type: research
In this study, we developed a high-throughput and multiplex IgG microsphere immunoassay (MIA) using the NS1 proteins of DENV1-DENV4, ZIKV and West Nile virus (WNV) to test samples from reverse-transcription-polymerase-chain reaction-confirmed cases, including primary DENV1, DENV2, DENV3, WNV and ZIKV infections, secondary DENV infection, and ZIKV infection with previous DENV infection. Combination of four DENV NS1 IgG MIAs revealed a sensitivity of 94.3% and specificity of 97.2% to detect DENV infection. The ZIKV and WNV NS1 IgG MIAs had a sensitivity/specificity of 100%/87.9% and 86.1%/78. 4%, respectively. A positive cor...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Malaria, Zika virus, West Nile virus, Dengue fever, and Lyme disease are common causes of morbidity and mortality around the world. While arthropod bites may cause local inflammation and discomfort, a greater concern is the potential to develop deadly systemic infection. Prevention of systemic infections by use of insect repellent (IR) constitutes one of the most critical aspects of public health efforts. Cost-effectiveness, availability, and high-efficacy against arthropod vectors are the key characteristics of an ideal IR.
Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
CONCLUSIONS: The co-circulation of those viruses in the same area represents a risk for the development of severe infections if they spread throughout the country. Successive flavivirus infections may have an impact on disease pathogenesis, as well as on the development of safe vaccine strategies. PMID: 31411310 [PubMed - in process]
Source: Memorias do Instituto Oswaldo Cruz - Category: Infectious Diseases Authors: Tags: Mem Inst Oswaldo Cruz Source Type: research
This report summarizes surveillance data reported to CDC for 2018 on nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses because they are primarily nondomestic viruses typically acquired through travel. In 2018, 48 states and the District of Columbia (DC) reported 2,813 cases of domestic arboviral disease, including 2,647 (94%) WNV disease cases. Of the WNV disease cases, 1,658 (63%) were classified as neuroinvasive disease (e.g., meningitis, encephalitis, and acute flaccid paralysis), for a national incidence of 0.51 cases of WNV neuroinvasive disease per 100,000 population. Because arbovi...
Source: MMWR Morb Mortal Wkl... - Category: Epidemiology Authors: Tags: MMWR Morb Mortal Wkly Rep Source Type: research
WEDNESDAY, July 17, 2019 -- Some mosquitoes spread diseases to humans through their bite, passing along harmful pathogens like Zika, dengue fever, West Nile virus and chikungunya. Now humans are turning the tables, infecting these dangerous...
Source: Drugs.com - Daily MedNews - Category: General Medicine Source Type: news
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