PubTransformer

A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Zika virus - Top 30 Publications

Inhibitors of the Histone Methyltransferases EZH2/1 Induce a Potent Antiviral State and Suppress Infection by Diverse Viral Pathogens.

Epigenetic regulation is based on a network of complexes that modulate the chromatin character and structure of the genome to impact gene expression, cell fate, and development. Thus, epigenetic modulators represent novel therapeutic targets used to treat a range of diseases, including malignancies. Infectious pathogens such as herpesviruses are also regulated by cellular epigenetic machinery, and epigenetic therapeutics represent a novel approach used to control infection, persistence, and the resulting recurrent disease. The histone H3K27 methyltransferases EZH2 and EZH1 (EZH2/1) are epigenetic repressors that suppress gene transcription via propagation of repressive H3K27me3-enriched chromatin domains. However, while EZH2/1 are implicated in the repression of herpesviral gene expression, inhibitors of these enzymes suppressed primary herpes simplex virus (HSV) infection in vitro and in vivo Furthermore, these compounds blocked lytic viral replication following induction of HSV reactivation in latently infected sensory ganglia. Suppression correlated with the induction of multiple inflammatory, stress, and antipathogen pathways, as well as enhanced recruitment of immune cells to in vivo infection sites. Importantly, EZH2/1 inhibitors induced a cellular antiviral state that also suppressed infection with DNA (human cytomegalovirus, adenovirus) and RNA (Zika virus) viruses. Thus, EZH2/1 inhibitors have considerable potential as general antivirals through the activation of cellular antiviral and immune responses.IMPORTANCE A significant proportion of the world's population is infected with herpes simplex virus. Primary infection and subsequent recurrent reactivation can result in diseases ranging from mild lesions to severe ocular or neurological damage. Herpesviruses are subject to epigenetic regulation that modulates viral gene expression, lytic replication, and latency-reactivation cycles. Thus, epigenetic pharmaceuticals have the potential to alter the course of infection and disease. Here, while the histone methyltransferases EZH2/1 are implicated in the suppression of herpesviruses, inhibitors of these repressors unexpectedly suppress viral infection in vitro and in vivo by induction of key components of cellular innate defense pathways. These inhibitors suppress infection by multiple viral pathogens, indicating their potential as broad-spectrum antivirals.

Zika Virus Research Models.

The 2015 Brazilian Zika virus outbreak sparked a rapid response to control the spread of the virus. What was first understood to be a mild self-resolving infection is now linked to significant neurological defects in both neonates, and adults. The WHO declared the 2016 Zika epidemic a public health emergency and issued an unprecedented recommendation to women in affected regions to delay pregnancy until the risks surrounding Zika virus could be understood, or the epidemic contained. Since that time, considerable effort has been dedicated to understanding Zika transmission and pathogenesis to aid the development of drugs and vaccines. Several models have emerged to study several facets of Zika biology; this review details the various model systems.

Viral Retinopathy in Experimental Models of Zika Infection.

Emerging evidence has shown that both congenital and adult Zika virus (ZIKV) infection can cause eye diseases. The goals of the current study were to explore mechanisms and pathophysiology of ZIKV-induced eye defects.

Examining Mosquito Surveillance and Control Capacity in the Top 10 Areas at Risk for Zika Virus Exposure in the United States.

Public sentiment and discourse about Zika virus on Instagram.

Social media have strongly influenced the awareness and perceptions of public health emergencies, and a considerable amount of social media content is now shared through images, rather than text alone. This content can impact preparedness and response due to the popularity and real-time nature of social media platforms. We sought to explore how the image-sharing platform Instagram is used for information dissemination and conversation during the current Zika outbreak.

Zika virus-induced neurological critical illness in Latin America: Severe Guillain-Barre Syndrome and encephalitis.

Zika virus (ZIKAV) is classically described as causing minor symptoms in adult patients, however neurologic complications have been recognized. The recent outbreak in Central and South America has resulted in serious illness in some adult patients. We report adult patients in Latin America diagnosed with ZIKAV infection admitted to Intensive Care Units (ICUs).

Zika Virus Disease in Children in Colombia, August 2015 to May 2016.

Children are considered a potentially vulnerable population for Zika virus infection. However, data on paediatric Zika virus infection are sparse.

The Expanding Spectrum of Zika Virus Infections of the Nervous System.

Neurologic Complications Associated With the Zika Virus in Brazilian Adults.

There are no prospective cohort studies assessing the incidence and spectrum of neurologic manifestations secondary to Zika virus (ZIKV) infection in adults.

Zika Virus in Ontario: Evaluating a Rapid Risk Assessment Tool.

Wolbachia-mediated virus blocking in the mosquito vector Aedes aegypti.

Viruses transmitted by mosquitoes such as dengue, Zika and West Nile cause a threat to global health due to increased geographical range and frequency of outbreaks. The bacterium Wolbachia pipientis may be the solution reducing disease transmission. Though commonly missing in vector species, the bacterium was artificially and stably introduced into Aedes aegypti to assess its potential for biocontrol. When infected with Wolbachia, mosquitoes become refractory to infection by a range of pathogens, including the aforementioned viruses. How the bacterium is conferring this phenotype remains unknown. Here we discuss current hypotheses in the field for the mechanistic basis of pathogen blocking and evaluate the evidence from mosquitoes and related insects.

What We Are Watching-Top Global Infectious Disease Threats, 2013-2016: An Update from CDC's Global Disease Detection Operations Center.

To better track public health events in areas where the public health system is unable or unwilling to report the event to appropriate public health authorities, agencies can conduct event-based surveillance, which is defined as the organized collection, monitoring, assessment, and interpretation of unstructured information regarding public health events that may represent an acute risk to public health. The US Centers for Disease Control and Prevention's (CDC's) Global Disease Detection Operations Center (GDDOC) was created in 2007 to serve as CDC's platform dedicated to conducting worldwide event-based surveillance, which is now highlighted as part of the "detect" element of the Global Health Security Agenda (GHSA). The GHSA works toward making the world more safe and secure from disease threats through building capacity to better "Prevent, Detect, and Respond" to those threats. The GDDOC monitors approximately 30 to 40 public health events each day. In this article, we describe the top threats to public health monitored during 2012 to 2016: avian influenza, cholera, Ebola virus disease, and the vector-borne diseases yellow fever, chikungunya virus, and Zika virus, with updates to the previously described threats from Middle East respiratory syndrome-coronavirus (MERS-CoV) and poliomyelitis.

Zika Virus (ZIKV): a review of proposed mechanisms of transmission and associated congenital abnormalities.

Zika virus (ZIKV) has been of major international public health concern following large outbreaks in the Americas occurring in 2015-2016. Most notably, ZIKV has been seen to pose dangers in pregnancy due to its association with congenital abnormalities such as microcephaly. Numerous experimental approaches have been taken to address how the virus can cross the placenta, alter normal fetal development, and disrupt specific cellular functions. Many areas concerning the mechanisms of transmission, especially from mother to fetus, are largely unknown but demand further research. Several promising new studies are presented that provide insight into possible mechanisms of transmission, different cell types affected, and immune responses towards the virus. By aiming to better understand the processes behind altered fetal neuronal development due to ZIKV infection, the hope is to find ways to increase protection of the fetus and prevent congenital abnormalities such as microcephaly. As ZIKV infection is spreading to increasingly more areas and bringing harmful outcomes and birth defects with it, it is imperative to identify the mechanisms of transmitting this infectious agent, consider different genetic backgrounds of hosts and strain types, and navigate methods to protect those affected from the detrimental effects of this newly emerging virus.

The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks zika virus replication.

Since the emergence of Zika virus (ZIKV) in Brazil in 2015, 48 countries and territories in the Americas have confirmed autochthonous cases of the disease caused by the virus. The ZIKV-associated neurological manifestations and congenital defects make the development of safe and effective antivirals against ZIKV of utmost importance. Here, we evaluated the antiviral activity of 6-methylmercaptopurine riboside (6MMPr), a thiopurine nucleoside analog derived from the prodrug azathioprine (AZA), against the epidemic ZIKV strain circulating in Brazil. In all the assays, an epithelial (Vero) and an human neuronal (SH-SY5Y) cell line were used to evaluate the cytotoxicity and the effective concentrations of 6MMPr against ZIKV. The levels of ZIKV RNA, viral infectious titer and the percentage of infected cells at the presence or absence of 6MMPr was used to determine the antiviral efficacy. We show that 6MMPr decreased ZIKV production by more than 99% in both cell lines in a dose- and time-dependent way. Interestingly, 6MMPr was 1.6 times less toxic to SH-SY5Y cells compared to Vero cells, presenting a 50% cytotoxic concentration (CC50) of 460.3 µM and 291 µM, respectively. The selectivity index of 6MMPr for Vero and SH-SY5Y cells was 11.9 and 22.7, respectively, highlighting the safety profile of the drug to neuronal cells. Taken together, our results identify, for the first time, the thiopurine nucleoside analog 6MMPr as promising antiviral candidate against ZIKV that warrants further in vivo evaluation.

Viral Hijacking of Formins in Neurodevelopmental Pathologies.

The 2015 Zika virus (ZIKV) outbreak caused global concern when it was determined to cause microcephaly, hearing loss, and other neurodevelopmental manifestations upon fetal exposure. Significant progress has been made in our understanding of the interactions between ZIKV and the pregnant host, but there is still a critical need to understand how ZIKV and other neurotropic viruses affect fetal neurodevelopment. Diaphanous-related formins (Diaphs) have recently been identified as microcephaly-associated proteins in humans and mice. Mutations in Diaphs affect the function of neural progenitor cells, much like prenatal viral infection. We present a novel hypothesis that viruses 'hijack' Diaphs in neural progenitor cells, causing autonomous differentiation and apoptosis of neural progenitor cells, which could potentially contribute to virus-associated neurological pathologies.

Zika Virus and Neurological Disease: Investing in Prevention.

Estimating the reproductive number, total outbreak size, and reporting rates for Zika epidemics in South and Central America.

As South and Central American countries prepare for increased birth defects from Zika virus outbreaks and plan for mitigation strategies to minimize ongoing and future outbreaks, understanding important characteristics of Zika outbreaks and how they vary across regions is a challenging and important problem. We developed a mathematical model for the 2015/2016 Zika virus outbreak dynamics in Colombia, El Salvador, and Suriname. We fit the model to publicly available data provided by the Pan American Health Organization, using Approximate Bayesian Computation to estimate parameter distributions and provide uncertainty quantification. The model indicated that a country-level analysis was not appropriate for Colombia. We then estimated the basic reproduction number to range between 4 and 6 for El Salvador and Suriname with a median of 4.3 and 5.3, respectively. We estimated the reporting rate to be around 16% in El Salvador and 18% in Suriname with estimated total outbreak sizes of 73,395 and 21,647 people, respectively. The uncertainty in parameter estimates highlights a need for research and data collection that will better constrain parameter ranges.

Zika Virus: An Emerging Worldwide Threat.

ZIKA virus (ZIKV) poses a severe threat to the world. Recent outbreaks of ZIKV after 2007 along with its quick transmission have made this virus a matter of international concern. The virus shows symptoms that are similar to those caused in the wake of dengue virus (DENV) and other flaviviruses, which makes it difficult to discern the viral infection. Diagnosis is further complicated as the virus cross-reacts with antibodies of other viruses. Currently, molecular diagnosis of the virus is being performed by RT-PCR and IgM-captured enzyme-linked immunosorbent assay (MAC-ELISA). The real brunt of the virus is, however, borne by children and adults alike. Case studies of the ZIKV outbreaks in the French Polynesia and other places have suggested that there is a close link between the ZIKV and Gullian-Barre syndrome (GBS). The GBS has closely followed in areas facing ZIKV outbreaks. Although solid evidence is yet to emerge, clinical data integration has revealed a large number of ZIKV patients having GBS. Moreover, the amniotic fluids, blood cord, and miscarriage tissues of mothers have been detected with ZIKV, which indicates that the virus either gets transferred from mother to fetus or seeks direct entry in the fetus, causing microcephaly and other brain anomalies in the newborn babies. Studies on mice have confirmed the link between the ZIKV infection during pregnancy and microcephaly in babies. Reports have highlighted the sexual transmission of the ZIKV, as it has been detected in the semen and saliva of affected persons. The intensity with which the ZIKA is spreading can collapse the health sector of several countries, which are poor. A comprehensive strategy is a need of an hour to combat this virus so as to prevent its transmission and avert the looming threat. At the same time, more research on the cure of the ZIKV is imperative.

Modeling the transmission and control of Zika in Brazil.

Zika virus, a reemerging mosquito-borne flavivirus, started spread across Central and Southern America and more recently to North America. The most serious impacted country is Brazil. Based on the transmission mechanism of the virus and assessment of the limited data on the reported suspected cases, we establish a dynamical model which allows us to estimate the basic reproduction number R 0 = 2.5020. The wild spreading of the virus make it a great challenge to public health to control and prevention of the virus. We formulate two control models to study the impact of releasing transgenosis mosquitoes (introducing bacterium Wolbachia into Aedes aegypti) on the transmission of Zika virus in Brazil. Our models and analysis suggest that simultaneously releasing Wolbachia-harboring female and male mosquitoes will achieve the target of population replacement, while releasing only Wolbachia-harboring male mosquitoes will suppress or even eradicate wild mosquitoes eventually. We conclude that only releasing male Wolbachia mosquitoes is a better strategy for control the spreading of Zika virus in Brazil.

Current status of therapeutic and vaccine approaches against Zika virus.

Zika virus (ZIKV) is a global threat because it is spreading at an alarming rate because of its wider range of transmission routes. The neuroteratogenic nature of ZIKV infection is posing serious threats to unborn lives therefore, it is necessary to develop an ideal ZIKV prophylactic or therapeutic agent urgently. Researchers are having tough time finding a treatment for ZIKV in part because of serious consequences of vaccines and drugs to unborn lives and pregnant women. However, in vitro and in vivo evaluation of therapeutic efficacy of DNA vaccine, recombinant subunit vaccine, and ZIKV purified inactivated vaccine offers hope for human protection. Large number of food and drug administration (FDA) approved drugs as wells as compounds with anti-ZIKV activity offer valuable opportunity to control the massive bio-burden of this catastrophic epidemic. Some evidences suggest that immunotherapeutics might prove to be winning strategy in pregnant females. Here, we review the recent advances and current knowledge regarding therapeutic interventions against ZIKV infection. This article will provide baseline data and roadmap to prosecute further research for the development of novel therapeutic strategy to curb the explosive rise in ZIKV.

Differential outcomes of Zika virus infection in Aedes aegypti orally challenged with infectious blood meals and infectious protein meals.

Infection of mosquitoes is an essential step for the transmission of mosquito-borne arboviruses in nature. Engorgement of infectious blood meals from viremic infected vertebrate hosts allows the entry of viruses and initiates infection of midgut epithelial cells. Historically, the infection process of arboviruses in mosquitoes has been studied through the engorgement of mosquitoes from viremic laboratory animals or from artificial feeders containing blood mixed with viruses harvested from cell cultures. The latter approach using so-called artificial blood meals is more frequently used since it is readily optimized to maximize viral titer, negates the use of animals and can be used with viruses for which there are no small animal models. Use of artificial blood meals has enabled numerous studies on mosquito infections with a wide variety of viruses; however, as described here, with suitable modification it can also be used to study the interplay between infection, specific blood components, and physiological consequences associated with blood engorgement. For hematophagous female mosquitoes, blood is the primary nutritional source supporting all physiological process including egg development, and also influences neurological processes and behaviors such as host-seeking. Interactions between these blood-driven vector biological processes and arbovirus infection that is mediated via blood engorgement have not yet been specifically studied. This is in part because presentation of virus in whole blood inevitably induces enzymatic digestion processes, hormone driven oogenesis, and other biological changes. In this study, the infection process of Zika virus (ZIKV) in Aedes aegypti was characterized by oral exposure via viral suspension meals within minimally bovine serum albumin complemented medium or within whole blood. The use of bovine serum albumin in infectious meals provides an opportunity to evaluate the role of serum albumin during the process of flavivirus infection in mosquitoes.

Notes from the Field: Zika Virus-Associated Neonatal Birth Defects Surveillance - Texas, January 2016-July 2017.

On November 28, 2016, the Texas Department of State Health Services (Texas DSHS) reported its first confirmed case of local mosquitoborne Zika virus transmission in the city of Brownsville, located in south Texas along the U.S.-Mexico border. Zika virus infection during pregnancy has been linked to adverse congenital outcomes including microcephaly, neural tube defects, early brain malformations, structural eye abnormalities, congenital deafness, and limb contractures (1). On January 1, 2016, Texas DSHS established enhanced surveillance to identify women with laboratory evidence of possible Zika virus infection during pregnancy and suspected cases of Zika virus-associated birth defects among completed pregnancies.

Zika virus and the eye.

The aim of this study was to review the ocular findings related to the Zika virus (ZIKV) based on the main studies published to date, describe the patterns of the lesions and risk factors, and identify the public health implications and scientific importance of this emerging disease.

Whole-genome sequence analysis of Zika virus, amplified from urine of traveler from the Philippines.

Zika virus (ZIKV) (genus Flavivirus, family Flaviviridae) is an emerging pathogen associated with microcephaly and Guillain-Barré syndrome. The rapid spread of ZIKV disease in over 60 countries and the large numbers of travel-associated cases have caused worldwide concern. Thus, intensified surveillance of cases among immigrants and tourists from ZIKV-endemic areas is important for disease control and prevention. In this study, using Next Generation Sequencing, we reported the first whole-genome sequence of ZIKV strain AFMC-U, amplified from the urine of a traveler returning to Korea from the Philippines. Phylogenetic analysis showed geographic-specific clustering. Our results underscore the importance of examining urine in the diagnosis of ZIKV infection.

Virus-like particles that display Zika virus envelope protein domain III induce potent neutralizing immune responses in mice.

Several Zika virus (ZIKV) vaccine candidates have recently been described which use inactivated whole virus, DNA or RNA that express the virus' Envelope (E) glycoprotein as the antigen. These were successful in stimulating production of virus-targeted antibodies that protected animals against ZIKV challenges, but their use potentially will predispose vaccinated individuals to infection by the related Dengue virus (DENV). We have devised a virus like particle (VLP) carrier based on the hepatitis B core antigen (HBcAg) that displays the ZIKV E protein domain III (zDIII), and shown that it can be produced quickly and easily purified in large quantities from Nicotiana benthamiana plants. HBcAg-zDIII VLPs are shown to be highly immunogenic, as two doses elicited potent humoral and cellular responses in mice that exceed the threshold correlated with protective immunity against multiple strains of Zika virus. Notably, HBcAg-zDIII VLPs-elicited antibodies did not enhance the infection of DENV in Fc gamma receptor-expressing cells, offsetting the concern of ZIKV vaccines inducing cross-reactive antibodies and sensitizing people to subsequent DENV infection. Thus, our zDIII-based vaccine offers improved safety and lower cost production than other current alternatives, with equivalent effectiveness.

A neutralization assay for Zika and Dengue viruses using a real-time PCR-based endpoint assessment.

The global spread and infective complications of Zika virus (ZKV) and Dengue virus (DENV) have made them flaviviruses of public health concern. Serological diagnosis can be challenging due to antibody cross-reactivity, particularly in secondary flavivirus infections or when there is a history of flavivirus vaccination. The virus neutralization assay is considered to be the most specific assay for measurement of anti-flavivirus antibodies. This study describes an assay where neutralization endpoint is measured by real-time PCR, providing results within 72 hours. It demonstrated 100% sensitivity (24/24 ZKV and 15/15 DENV) and 100% specificity (11/11 specimens) when testing well-characterised sera. In addition, the assay was able to determine the correct DENV serotype in 91.7% of cases. The high sensitivity and specificity of the real-time PCR neutralization assay makes it suitable to use as a confirmatory test for sera that are reactive in commercial IgM/IgG enzyme immunoassays. Results are objective and the PCR-based measurement of neutralisation endpoint lends itself to automation so that throughput may be increased in times of high demand.

Development of Virus like Particle Vaccine and Reporter Assay for Zika Virus.

Recent worldwide outbreaks of Zika virus (ZIKV) infection and the lack of an approved vaccine raises serious concerns regarding preparedness to combat this emerging virus. We used a Virus Like Particle (VLP) based approach to develop a vaccine and a microneutralization assay against ZIKV. Synthetic C-prM-E (Capsid-preMembrane-Envelope) gene construct of ZIKV was used to generate Reporter Virus Particles (RVPs) that package GFP reporter expressing WNV replicon. The assay was adapted to 96 well format, similar to the Plaque Reduction Neutralization Test (PRNT) and showed high reproducibility with specific detection of ZIKV neutralizing antibodies. Furthermore, C-prM-E and prM-E VLPs were tested as vaccine candidates in mice and compared to DNA vaccination. While ZIKV prM-E construct alone was sufficient for generating VLPs; efficient VLP production from the C-prM-E construct could be achieved in the presence of WNV NS2B-3 protease that cleaves C from prM allowing virus release. Immunization studies in mice showed that VLPs generated higher neutralizing antibody titers than DNA vaccine with C-prM-E VLPs slightly better than prM-E VLPs. The superiority of C-prM-E VLPs suggests that inclusion of capsid may have benefits for ZIKV and other flaviviral VLP vaccines. To facilitate the VLP platform, we generated a stable cell line expressing high levels of ZIKV prM-E proteins that constitutively produce VLPs as well as a cell line expressing ZIKV C-prM-E proteins for RVP production. While several vaccine platforms have been proposed for ZIKV, this study describes a safe, effective and economical VLP based vaccine against ZIKV.IMPORTANCE To address the growing Zika virus epidemic we undertook this study with two objectives. Firstly, to develop a safe effective and economical vaccine for ZIKV and secondly, to develop a rapid versatile assay to detect anti-ZIKV immune response. We generated cell lines stably expressing the ZIKV prM-E that produce high amounts of VLPs in the supernatants and ZIKV C-prM-E cell line that produces reporter virus particles upon transfection with GFP replicon plasmid. The prM-E VLPs induced a strong neutralizing antibody response in mice that was better when the capsid was included. VLP based vaccines showed significantly better neutralizing antibody response when compared to their DNA counterparts. The RVP based microneutralization assay worked similar to the PRNT assay with a rapid GFP readout in a 96 well format. Our VLP based platform provides a source for ZIKV vaccine and diagnosis that can be rapidly adapted to current outbreaks.

Rapid Detection of Infectious Envelope Proteins by Magnetoplasmonic Toroidal Metasensors.

Unconventional characteristics of magnetic toroidal multipoles have triggered researchers to study these unique resonant phenomena by using both 3D and planar resonators under intense radiation. Here, going beyond conventional planar unit cells, we report on the observation of magnetic toroidal modes using artificially engineered multi-metallic planar plasmonic resonators. The proposed micro-structures consist of iron (Fe) and titanium (Ti) components acting as magnetic resonators and torus, respectively. Our numerical studies and following experimental verifications show that the proposed structures allow for excitation of toroidal dipoles in the terahertz (THz) domain with the experimental Q-factor of ~18. Taking the advantage of high-Q toroidal lineshape and its dependence on the environmental perturbations, we demonstrate that room-temperature toroidal metasurface is a reliable platform for immunosensing applications. As a proof of concept, we utilized our plasmonic metasurface to detect Zika-virus (ZIKV) envelope protein (with diameter of 40 nm) using a specific ZIKV antibody. The sharp toroidal resonant modes of the surface functionalized structures shift as a function of the ZIKV envelope protein for small concentrations (~ pM). The results of sensing experiments reveal rapid, accurate and quantitative detection of envelope proteins with the limit of detection of ~24.2 pg/mL and sensitivity of 6.47 GHz/log(pg/mL). We envision that the proposed toroidal metasurface opens new avenues for developing low-cost, and efficient THz plasmonic sensors for infection and targeted bio-agent detection.

EVIDENCE OF INCREASING DIVERSIFICATION OF ZIKA VIRUS STRAINS ISOLATED IN THE AMERICAN CONTINENT.

Zika virus (ZIKV) is a member of the family Flaviviridae. ZIKV emerged in Brazil in 2015, causing an unprecedented epidemic and since then the virus has rapidly spread throughout the Americas. These facts highlight the need of detailed phylogenetic studies to understand the emergence, spread and evolution of ZIKV populations. For these reasons, a Bayesian coalescent Markov Chain Monte Carlo analysis of complete genome sequences of ZIKV strains recently isolated in the American continent was performed. The results of these studies revealed an increasing diversification of ZIKV strains in different genetic lineages and co-circulation of distinct genetic lineages in several countries in the region. The time of the most recent common ancestor (tMRCA) was established to be around February 20(th) , 2014 for ZIKV strains circulating in the American region. A mean rate of evolution of 1.55 × 10(-3) substitutions/site/year was obtained for ZIKV strains included in this study. A Bayesian skyline plot indicate a sharp increase in population size from February, 2014 to July 2015 and a decline during 2016. These results are discussed in terms of the emergence and evolution of ZIKV populations in the American continent. This article is protected by copyright. All rights reserved.

Zika virus replication in the mosquito Culex quinquefasciatus in Brazil.

Zika virus (ZIKV) is a flavivirus that has recently been associated with an increased incidence of neonatal microcephaly and other neurological disorders. The virus is primarily transmitted by mosquito bite, although other routes of infection have been implicated in some cases. The Aedes aegypti mosquito is considered to be the main vector to humans worldwide; however, there is evidence that other mosquito species, including Culex quinquefasciatus, transmit the virus. To test the potential of Cx. quinquefasciatus to transmit ZIKV, we experimentally compared the vector competence of laboratory-reared Ae. aegypti and Cx. quinquefasciatus. Interestingly, we were able to detect the presence of ZIKV in the midgut, salivary glands and saliva of artificially fed Cx. quinquefasciatus. In addition, we collected ZIKV-infected Cx. quinquefasciatus from urban areas with high microcephaly incidence in Recife, Brazil. Corroborating our experimental data from artificially fed mosquitoes, ZIKV was isolated from field-caught Cx. quinquefasciatus, and its genome was partially sequenced. Collectively, these findings indicate that there may be a wider range of ZIKV vectors than anticipated.