Viral Determinants and Vector Competence of Zika Virus Transmission

Tham, Hong Wai; Balasubramaniam, Vinod; Ooi, Man Kwan; Chew, Miaw Fang

doi:10.3389/fmicb.2018.01040

Cited by 24 publications

(17 citation statements)

References 137 publications

(165 reference statements)

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“…49 DENV affects 390 million people worldwide each year (Bhatt et al, 2013). ZIKV, another 50 arbovirus with significant health impacts, was originally confined to small outbreaks, but 51 expanded rapidly to over 30 countries between 2015 and 2016 (Tham et al, 2018). 52…”

Section: Introduction 39mentioning

confidence: 99%

Insulin potentiates JAK/STAT signaling to broadly inhibit flavivirus replication in insect vectors

Ahlers

Trammell

Carrell

et al. 2019

Preprint

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SUMMARYThe World Health Organization estimates that over half of the world’s population is at risk for vector-borne diseases, such as those caused by arboviral infection. Because many arboviruses are mosquito-borne, investigation of the insect immune response will help identify targets that could reduce the spread of these viruses by the mosquito. In this study, we used a genetic screening approach to identify insulin-like receptor as a novel component of the immune response to arboviral infection. We determined 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 showed that insulin signaling activates the JAK/STAT, but not RNAi, pathway to control infection. Finally, we validated 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 emerging human pathogens.

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Section: Introduction 39mentioning

confidence: 99%

Insulin potentiates JAK/STAT signaling to broadly inhibit flavivirus replication in insect vectors

Ahlers

Trammell

Carrell

et al. 2019

Preprint

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“…The ORF codes a single polyprotein that is processed and cut to yield 3 structural proteins: C→ capsid, prM→ pre-membrane, E→ envelope and 7 non-structural proteins: NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5 [2,3]. Similar to other arboviruses, ZIKV infects humans mainly via the bite of an infected female Aedes mosquito while it can be also maintained in sylvatic cycles (transmission between mosquitoes and wild animals) [4][5][6][7]. The virus incubates for 5-10 days in the mosquito's midgut before invading the salivary glands thus infecting its next host as the mosquito feeds [8,9].…”

Section: Introductionmentioning

confidence: 99%

Importance of Zika Virus NS5 Protein for Viral Replication

2019

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Zika virus is the latest addition to an ever-growing list of arboviruses that are causing outbreaks with serious consequences. A few mild cases were recorded between 1960 and 1980 until the first major outbreak in 2007 on Yap Island. This was followed by more severe outbreaks in French Polynesia (2013) and Brazil (2015), which significantly increased both Guillain-Barre syndrome and microcephaly cases. No current vaccines or treatments are available, however, recent studies have taken interest in the NS5 protein which encodes both the viral methyltransferase and RNA-dependent RNA polymerase. This makes it important for viral replication alongside other important functions such as inhibiting the innate immune system thus ensuring virus survival and replication. Structural studies can help design inhibitors, while biochemical studies can help understand the various mechanisms utilized by NS5 thus counteracting them might inhibit or abolish the viral infection. Drug repurposing targeting the NS5 protein has also proven to be an effective tool since hundreds of thousands of compounds can be screened therefore saving time and resources, moreover information on these compounds might already be available especially if they are used to treat other ailments.

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“…Human health concerns posed by ZIKV are further aggravated due to the non-vector-borne transmission of ZIKV. The virus is spread to people primarily through the bite of infected mosquitoes of the genus Aedes [ 20 , 21 ], however, at difference to most other flaviviruses, ZIKV can also be transmitted from mother to child during pregnancy or spread through sexual contact, breastfeeding, blood transfusion, and non-human primate bites [ 1 , 22 , 23 ]. Due to the recent emergence of ZIKV as an important human pathogen, there are not currently approved vaccines or antivirals available to combat ZIKV infection.…”

Section: Introductionmentioning

confidence: 99%

An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo

Márquez-Jurado

Nogales

Ávila‐Pérez

et al. 2018

Viruses

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The recent outbreaks of Zika virus (ZIKV), its association with Guillain–Barré syndrome and fetal abnormalities, and the lack of approved vaccines and antivirals, highlight the importance of developing countermeasures to combat ZIKV disease. In this respect, infectious clones constitute excellent tools to accomplish these goals. However, flavivirus infectious clones are often difficult to work with due to the toxicity of some flavivirus sequences in bacteria. To bypass this problem, several alternative approaches have been applied for the generation of ZIKV clones including, among others, in vitro ligation, insertions of introns and using infectious subgenomic amplicons. Here, we report a simple and novel DNA-launched approach based on the use of a bacterial artificial chromosome (BAC) to generate a cDNA clone of Rio Grande do Norte Natal ZIKV strain. The sequence was identified from the brain tissue of an aborted fetus with microcephaly. The BAC clone was fully stable in bacteria and the infectious virus was efficiently recovered in Vero cells through direct delivery of the cDNA clone. The rescued virus yielded high titers in Vero cells and was pathogenic in a validated mouse model (A129 mice) of ZIKV infection. Furthermore, using this infectious clone we have generated a mutant ZIKV containing a single amino acid substitution (A175V) in the NS2A protein that presented reduced viral RNA synthesis in cell cultures, was highly attenuated in vivo and induced fully protection against a lethal challenge with ZIKV wild-type. This BAC approach provides a stable and reliable reverse genetic system for ZIKV that will help to identify viral determinants of virulence and facilitate the development of vaccine and therapeutic strategies.

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Viral Determinants and Vector Competence of Zika Virus Transmission

Cited by 24 publications

References 137 publications

Insulin potentiates JAK/STAT signaling to broadly inhibit flavivirus replication in insect vectors

Insulin potentiates JAK/STAT signaling to broadly inhibit flavivirus replication in insect vectors

Importance of Zika Virus NS5 Protein for Viral Replication

An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo

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