In vitro and in silico Models to Study Mosquito-Borne Flavivirus Neuropathogenesis, Prevention, and Treatment
Mosquito-borne flaviviruses can cause disease in the nervous system, resulting in a significant burden of morbidity and mortality. Disease models are necessary to understand neuropathogenesis and identify potential therapeutics and vaccines. Non-human primates have been used extensively but present major challenges. Advances have also been made towards the development of humanized mouse models, but these models still do not fully represent human pathophysiology. Recent developments in stem cell technology and cell culture techniques have allowed the development of more physiologically relevant human cell-based models. In silico modeling has also allowed researchers to identify and predict transmission patterns and discover potential vaccine and therapeutic candidates. This review summarizes the research on in vitro and in silico models used to study three mosquito-borne flaviviruses that cause neurological disease in humans: West Nile, Dengue, and Zika. We also propose a roadmap for 21st century research on mosquito-borne flavivirus neuropathogenesis, prevention, and treatment.
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.
Publication date: Available online 16 August 2019Source: MicronAuthor(s): Lilian Mirian Oliveira de Morais, Eduardo Inocente Jussiani, João Antonio Cyrino Zequi, Paulo José dos Reis, Avacir Casanova AndrelloAbstractAedes aegypti and Aedes albopictus are vectors of several arboviruses responsible for causing dengue, chikungunya, Zika, and yellow fever viruses and microcephaly, resulting in a public health problem in several countries worldwide. Even in this scenario, studies on the morphology of mosquito eggs are still lacking. In this paper, X-ray microtomography was used to study mosquito egg morphology. Sev...
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]
This study defines grp94 as a crucial host factor for flavivirus replication and identified CDDO-me as a potent small molecule inhibitor of flavivirus infection. Inhibition of grp94 may contribute to the antiviral activity of CDDO-me. Further investigation of grp94 inhibitors may lead to a new class of broad-spectrum anti-flaviviral medications.
Conclusions: The results showed that the network topology exhibits the features of a scale-free network instead of a random network. Focal hubs are highlighted and the critical period is found. Outcomes are important for the researchers, health officials, and policy makers who deal with arbovirus epidemic diseases. Zika virus and Chikungunya virus can also be modelled and analyzed in this manner. PMID: 31406610 [PubMed]
Source: World Health Organization (WHO). Published: 8/14/2019. This 25-minute video features live responses from an expert to questions about dengue, which is transmitted through Aedes aegypti and Aedes Albopictus mosquitoes, also known as Asian tiger mosquitoes. These are the same mosquitoes that transmit chikungunya, yellow fever, and Zika. Topics include identifying the warning signs and symptoms of severe dengue, and complications caused by dengue. (Video or Multimedia)
This study defines grp94 as a crucial host factor for flavivirus replication and identified CDDO-me as a potent small molecule inhibitor of flavivirus infection. Inhibition of grp94 may contribute to the antiviral activity of CDDO-me. Further investigation of grp94 inhibitors may lead to a new class of broad-spectrum anti-flaviviral medications. PMID: 31421166 [PubMed - as supplied by publisher]
Conclusions/SignificanceThe two barriers associated withAe.aegypti midgut prevent YFV-17D replication. Our study contributes to our basic understanding of vector –pathogen interactions and may also aid in the development of non-transmissible live virus vaccines.
CONCLUSION: This study identified an asymptomatic ZIKV infection in a blood donor occurring before those previously recognized by blood donation screening. NAT and PR continue to be used as acceptable strategies to prevent transfusion-transmitted arboviral infections worldwide; however, repeated arboviral outbreaks warrant consideration of PR as a more proactive approach. PMID: 31407817 [PubMed - as supplied by publisher]
Authors: Slavov SN, Ferreira FU, Rodrigues ES, Gomes R, Covas DT, Kashima S Abstract During zika and dengue viruse (ZIKV and DENV) outbreaks, the majority of the infected individuals remain clinically asymptomatic. Such asymptomatic individuals may occasionally acquire both arboviruses, donate blood, and contaminate haemoderivatives. The aim of this study was to characterize a ZIKV/DENV-4 coinfection in asymptomatic blood donor who donated blood during a large mixed ZIKV/DENV outbreak in the Säo Paulo State, Brazil. On the basis of post-donation information, one blood donor sample was found positive for ZIKV a...