Characterization of Two Highly Specific Monoclonal Antibodies Targeting the Glycan Loop of the Zika Virus Envelope Protein.

Zika virus (ZIKV) is an emerging flavivirus associated with several neurological diseases such as Guillain-Barré syndrome in adults and microcephaly in newborn children. Its distribution and mode of transmission (via Aedes aegypti and Aedes albopictus mosquitoes) collectively cause ZIKV to be a serious concern for global health. High genetic homology of flaviviruses and shared ecology is a hurdle for accurate detection. Distinguishing infections caused by different viruses based on serological recognition can be misleading as many anti-flavivirus monoclonal antibodies (mAbs) discovered to date are highly cross-reactive, especially those against the envelope (E) protein. To provide more specific research tools, we produced ZIKV E directed hybridoma cell lines and characterized two highly ZIKV-specific mAb clones (mAbs A11 and A42) against several members of the Flavivirus genus. Epitope mapping of mAb A11 revealed glycan loop specificity in Domain I of the ZIKV E protein. The development of two highly specific mAbs targeting the surface fusion protein of ZIKV presents a significant advancement in research capabilities as these can be employed as essential tools to enhance our understanding of ZIKV identification on infected cells ex vivo or in culture.

HR-MAS NMR Metabolomics Profile of Vero Cells under the Influence of Virus Infection and nsP2 Inhibitor: A Chikungunya Case Study.

The arbovirus Chikungunya (CHIKV) is transmitted by Aedes mosquitoes in urban environments, and in humans, it triggers debilitating symptoms involving long-term complications, including arthritis and Guillain-Barré syndrome. The development of antiviral therapies is relevant, as no efficacious vaccine or drug has yet been approved for clinical application. As a detailed map of molecules underlying the viral infection can be obtained from the metabolome, we validated the metabolic signatures of Vero E6 cells prior to infection (CC), following CHIKV infection (CV) and also upon the inclusion of the nsP2 protease inhibitor wedelolactone (CWV), a coumestan which inhibits viral replication processes. The metabolome groups evidenced significant changes in the levels of lactate, myo-inositol, phosphocholine, glucose, betaine and a few specific amino acids. This study forms a preliminary basis for identifying metabolites through HR-MAS NMR (High Resolution Magic Angle Spinning Nuclear Magnetic Ressonance Spectroscopy) and proposing the affected metabolic pathways of cells following viral infection and upon incorporation of putative antiviral molecules.

Insights into Zika Virus Pathogenesis and Potential Therapeutic Strategies.

Zika virus (ZIKV) has emerged as a significant public health threat, reaching pandemic levels in 2016. Human infection with ZIKV can manifest as either asymptomatic or as an acute illness characterized by symptoms such as fever and headache. Moreover, it has been associated with severe neurological complications in adults, including Guillain-Barre syndrome, and devastating fetal abnormalities, like microcephaly. The primary mode of transmission is through Aedes spp. mosquitoes, and with half of the world's population residing in regions where Aedes aegypti, the principal vector, thrives, the reemergence of ZIKV remains a concern. This comprehensive review provides insights into the pathogenesis of ZIKV and highlights the key cellular pathways activated upon ZIKV infection. Additionally, we explore the potential of utilizing microRNAs (miRNAs) and phytocompounds as promising strategies to combat ZIKV infection.

Broad-Spectrum Antiviral Effect of Cannabidiol Against Enveloped and Nonenveloped Viruses.

Introduction: Cannabidiol (CBD), the main non-psychoactive cannabinoid of the Cannabis sativa plant, is a powerful antioxidant compound that in recent years has increased interest due to causes effects in a wide range of biological functions. Zika virus (ZIKV) is a virus transmitted mainly by the Aedes aegypti mosquitoes, which causes neurological diseases, such as microcephaly and Guillain-Barre syndrome. Although the frequency of viral outbreaks has increased recently, no vaccinations or particular chemotherapeutic treatments are available for ZIKV infection. Objectives: The major aim of this study was to explore the in vitro antiviral activity of CBD against ZIKV, expanding also to other dissimilar viruses. Materials and Methods: Cell cultures were infected with enveloped and nonenveloped viruses and treated with non-cytotoxic concentrations of CBD and then, viral titers were determined. Additionally, the mechanism of action of the compound during ZIKV in vitro infections was studied. To study the possible immunomodulatory role of CBD, infected and uninfected Huh-7 cells were exposed to 10 µM CBD during 48 h and levels of interleukins 6 and 8 and interferon-beta (IFN-ß) expression levels were measured. On the other hand, the effect of CBD on cellular membranes was studied. For this, an immunofluorescence assay was performed, in which cell membranes were labeled with wheat germ agglutinin. Finally, intracellular cholesterol levels were measured. Results: CBD exhibited a potent antiviral activity against all the tested viruses in different cell lines with half maximal effective concentration values (CE50) ranging from 0.87 to 8.55 µM. Regarding the immunomodulatory effect of CBD during ZIKV in vitro infections, CBD-treated cells exhibited significantly IFN-ß increased levels, meanwhile, interleukins 6 and 8 were not induced. Furthermore, it was determined that CBD affects cellular membranes due to the higher fluorescence intensity that was observed in CBD-treated cells and lowers intracellular cholesterol levels, thus affecting the multiplication of ZIKV and other viruses. Conclusions: It was demonstrated that CBD inhibits structurally dissimilar viruses, suggesting that this phytochemical has broad-spectrum antiviral effect, representing a valuable alternative in emergency situations during viral outbreaks, like the one caused by severe acute respiratory syndrome coronavirus 2 in 2020.

Identification of immunodominant T cell epitopes induced by natural Zika virus infection.

Zika virus (ZIKV) is a flavivirus primarily transmitted by Aedes species mosquitoes, first discovered in Africa in 1947, that disseminated through Southeast Asia and the Pacific Islands in the 2000s. The first ZIKV infections in the Americas were identified in 2014, and infections exploded through populations in Brazil and other countries in 2015/16. ZIKV infection during pregnancy can cause severe brain and eye defects in offspring, and infection in adults has been associated with higher risks of Guillain-Barré syndrome. We initiated a study to describe the natural history of Zika (the disease) and the immune response to infection, for which some results have been reported. In this paper, we identify ZIKV-specific CD4+ and CD8+ T cell epitopes that induce responses during infection. Two screening approaches were utilized: an untargeted approach with overlapping peptide arrays spanning the entire viral genome, and a targeted approach utilizing peptides predicted to bind human MHC molecules. Immunoinformatic tools were used to identify conserved MHC class I supertype binders and promiscuous class II binding peptide clusters predicted to bind 9 common class II alleles. T cell responses were evaluated in overnight IFN-γ ELISPOT assays. We found that MHC supertype binding predictions outperformed the bulk overlapping peptide approach. Diverse CD4+ T cell responses were observed in most ZIKV-infected participants, while responses to CD8+ T cell epitopes were more limited. Most individuals developed a robust T cell response against epitopes restricted to a single MHC class I supertype and only a single or few CD8+ T cell epitopes overall, suggesting a strong immunodominance phenomenon. Noteworthy is that many epitopes were commonly immunodominant across persons expressing the same class I supertype. Nearly all of the identified epitopes are unique to ZIKV and are not present in Dengue viruses. Collectively, we identified 31 immunogenic peptides restricted by the 6 major class I supertypes and 27 promiscuous class II epitopes. These sequences are highly relevant for design of T cell-targeted ZIKV vaccines and monitoring T cell responses to Zika virus infection and vaccination.

Dengue Fever-Induced Hypokalemic Paralysis in a Pregnant Patient: An Uncommon Presentation of a Common Disease.

Dengue fever is a globally prevalent, viral disease transmitted by Aedes mosquitoes, which is becoming increasingly common and can cause a range of symptoms, including fever, flu-like symptoms, and circulatory failure. Although it is classified as a non-neurotropic virus, research has suggested that dengue fever can also affect the nervous system and lead to conditions such as myositis, Guillain-Barré syndrome, or hypokalemic paralysis. We describe a case study of a young pregnant female with dengue-associated hypokalemic paralysis, who made a full recovery within 48 hours of receiving potassium supplementation. The case underscores the importance of recognizing and treating neurological complications of dengue fever promptly, particularly in areas where the disease is prevalent.

Infecção por Zika virus

A viral disease transmitted by the bite of AEDES mosquitoes infected with ZIKA VIRUS. Its mild DENGUE-like symptoms include fever, rash, headaches and ARTHRALGIA. The viral infection during pregnancy, in rare cases, is associated with congenital brain and ocular abnormalities, called Congenital Zika Syndrome, including MICROCEPHALY and may also lead to GUILLAIN-BARRE SYNDROME.

Enfermedad viral transmitida por la picadura de los mosquitos AEDES infectados con el VIRUS ZIKA. Sus síntomas leves similares al DENGUE incluyen fiebre, erupción cutánea, dolores de cabeza y ARTRALGIA. La infección viral durante el embarazo, en casos raros, está asociada a anormalidades cerebrales y oculares congénitas, llamadas Sindrome Congénito Zika, que incluyen MICROCEFALIA y también puede conducir al SÍNDROME DE GUILLAIN-BARRÉ.

Doença viral transmitida pela picada de mosquitos AEDES infectados com ZIKA VIRUS. Seus sintomas leves semelhantes à DENGUE incluem febre, erupção cutânea, dores de cabeça e ARTRALGIA. A infecção viral durante a gravidez, em raros casos, está associada com anomalias congênitas oculares e do encéfalo, chamadas de Síndrome de Zika Congênita, incluindo MICROCEFALIA e também pode levar a SÍNDROME DE GUILLAIN-BARRE.

Modeling the spread of the Zika virus by sexual and mosquito transmission.

Zika Virus (ZIKV) is a flavivirus that is transmitted predominantly by the Aedes species of mosquito, but also through sexual contact, blood transfusions, and congenitally from mother to child. Although approximately 80% of ZIKV infections are asymptomatic and typical symptoms are mild, multiple studies have demonstrated a causal link between ZIKV and severe diseases such as Microcephaly and Guillain Barré Syndrome. Two goals of this study are to improve ZIKV models by considering the spread dynamics of ZIKV as both a vector-borne and sexually transmitted disease, and also to approximate the degree of under-reporting. In order to accomplish these objectives, we propose a compartmental model that allows for the analysis of spread dynamics as both a vector-borne and sexually transmitted disease, and fit it to the ZIKV incidence reported to the National System of Public Health Surveillance in 27 municipalities of Colombia between January 1 2015 and December 31 2017. We demonstrate that our model can represent the infection patterns over this time period with high confidence. In addition, we argue that the degree of under-reporting is also well estimated. Using the model we assess potential viability of public health scenarios for mitigating disease spread and find that targeting the sexual pathway alone has negligible impact on overall spread, but if the proportion of risky sexual behavior increases then it may become important. Targeting mosquitoes remains the best approach of those considered. These results may be useful for public health organizations and governments to construct and implement suitable health policies and reduce the impact of the Zika outbreaks.

Zika virus as an emerging arbovirus of international public health concern.

Zika virus (ZIKV) was identified in 1947 in a rhesus monkey during an investigation of the yellow fever virus in the Zika Forest of Uganda; it was also isolated later from humans in Nigeria. The main distribution areas of ZIKV were the African mainland and South-East Asia in the 1980s, Micronesia in 2007, and more recently the Americas in 2014. ZIKV belongs to the Flaviviridae family and Flavivirus genus. ZIKV infection, which is transmitted by Aedes mosquitoes, is an emerging arbovirus disease. The clinical symptoms of ZIKV infection are fever, headache, rashes, arthralgia, and conjunctivitis, which clinically resemble dengue fever syndrome. Sometimes, ZIKV infection has been associated with Guillain-Barré syndrome and microcephaly. At the end of 2015, following an increase in cases of ZIKV infection associated with Guillain-Barré syndrome and microcephaly in newborns in Brazil, the World Health Organization declared a global emergency. Therefore, considering the global distribution and pathogenic nature of this virus, the current study aimed at reviewing the virologic features, transmission patterns, clinical manifestations, diagnosis, treatment, and prevention of ZIKV infection.

Association of Midgut Bacteria and Their Metabolic Pathways with Zika Infection and Insecticide Resistance in Colombian Aedes aegypti Populations.

INTRODUCTION: Aedes aegypti is the vector of several arboviruses such as dengue, Zika, and chikungunya. In 2015-16, Zika virus (ZIKV) had an outbreak in South America associated with prenatal microcephaly and Guillain-Barré syndrome. This mosquito's viral transmission is influenced by microbiota abundance and diversity and its interactions with the vector. The conditions of cocirculation of these three arboviruses, failure in vector control due to insecticide resistance, limitations in dengue management during the COVID-19 pandemic, and lack of effective treatment or vaccines make it necessary to identify changes in mosquito midgut bacterial composition and predict its functions through the infection. Its study is fundamental because it generates knowledge for surveillance of transmission and the risk of outbreaks of these diseases at the local level. METHODS: Midgut bacterial compositions of females of Colombian Ae. aegypti populations were analyzed using DADA2 Pipeline, and their functions were predicted with PICRUSt2 analysis. These analyses were done under the condition of natural ZIKV infection and resistance to lambda-cyhalothrin, alone and in combination. One-step RT-PCR determined the percentage of ZIKV-infected females. We also measured the susceptibility to the pyrethroid lambda-cyhalothrin and evaluated the presence of the V1016I mutation in the sodium channel gene. RESULTS: We found high ZIKV infection rates in Ae. aegypti females from Colombian rural municipalities with deficient water supply, such as Honda with 63.6%. In the face of natural infection with an arbovirus such as Zika, the diversity between an infective and non-infective form was significantly different. Bacteria associated with a state of infection with ZIKV and lambda-cyhalothrin resistance were detected, such as the genus Bacteroides, which was related to functions of pathogenicity, antimicrobial resistance, and bioremediation of insecticides. We hypothesize that it is a vehicle for virus entry, as it is in human intestinal infections. On the other hand, Bello, the only mosquito population classified as susceptible to lambda-cyhalothrin, was associated with bacteria related to mucin degradation functions in the intestine, belonging to the Lachnospiraceae family, with the genus Dorea being increased in ZIKV-infected females. The Serratia genus presented significantly decreased functions related to phenazine production, potentially associated with infection control, and control mechanism functions for host defense and quorum sensing. Additionally, Pseudomonas was the genus principally associated with functions of the degradation of insecticides related to tryptophan metabolism, ABC transporters with a two-component system, efflux pumps, and alginate synthesis. CONCLUSIONS: Microbiota composition may be modulated by ZIKV infection and insecticide resistance in Ae. aegypti Colombian populations. The condition of resistance to lambda-cyhalothrin could be inducing a phenome of dysbiosis in field Ae. aegypti affecting the transmission of arboviruses.

Understanding the Tissue Specificity of ZIKV Infection in Various Animal Models for Vaccine Development.

Zika virus (ZIKV) is an arthropod-borne virus that belongs to the Flavivirus genus and is principally transmitted by Aedes aegypti mosquitoes. ZIKV infection often causes no or only mild symptoms, but it can also trigger severe consequences, including microcephaly in infants and Guillain-Barré syndrome, uveitis, and neurologic manifestations in adults. There is no ZIKV vaccine or treatment currently approved for clinical use. The primary target of ZIKV infection has been recognized as the maternal placenta, with vertical transmission to the fetal brain. However, ZIKV can also spread to multiple tissues in adults, including the sexual organs, eyes, lymph nodes, and brain. Since numerous studies have indicated that there are slightly different tissue-specific pathologies in each animal model of ZIKV, the distinct ZIKV tropism of a given animal model must be understood to enable effective vaccine development. Here, we comprehensively discussed the tissue specificity of ZIKV reported in each animal model depending on the genetic background and route of administration. This review should facilitate the selection of appropriate animal models when studying the fundamental pathogenesis of ZIKV infection, thereby supporting the design of optimal preclinical and clinical studies for the development of vaccines and therapeutics.

Evidence of Spreading Zika Virus Infection Caused by Males of Different Species.

Zika virus (ZIKV) is a positive-sense single-stranded RNA flavivirus and is mainly transmitted by Aedes mosquitoes. This arbovirus has had a significant impact on health in recent years by causing malformations, such as microcephaly in babies and Guillain-Barré syndrome in adults. Some evidence indicates that ZIKV can be sexually transmitted and may persist in the male reproductive tract for an extended period in humans. Knockout and vasectomized mice have been used as models to reveal ZIKV infection in the male reproductive tract as a virus source. ZIKV presence in male and female mosquito reproductive tracts and eggs point to venereal and vertical/transovarian transmission, again demonstrating that the reproductive tract can be involved in the spread of ZIKV. Moreover, eggs protected by eggshells have the potential to be a ZIKV reservoir. Given the +-lack of vaccines and therapies for Zika fever and the underestimated prevalence rate, an understanding of ZIKV infection and its spread from the reproductive tract, which is protected from the immune system and potentially active for virus transmission, is imperative. We must also develop cheaper, more efficient techniques for virological surveillance inside vectors and humans, control vectors with ecofriendly insecticides, and promote condom use to avoid ZIKV contamination during sexual intercourse, as recommended by the World Health Organization.

Zika Virus Exploits Lipid Rafts to Infect Host Cells.

Several flaviviruses such as Hepatitis C virus, West Nile virus, Dengue virus and Japanese Encephalitis virus exploit the raft platform to enter host cells whereas the involvement of lipid rafts in Zika virus-host cell interaction has not yet been demonstrated. Zika virus disease is caused by a flavivirus transmitted by Aedes spp. Mosquitoes, although other mechanisms such as blood transfusion, sexual and maternal-fetal transmission have been demonstrated. Symptoms are generally mild, such as fever, rash, joint pain and conjunctivitis, but neurological complications, including Guillain-Barré syndrome, have been associated to this viral infection. During pregnancy, it can cause microcephaly and other congenital abnormalities in the fetus, as well as pregnancy complications, representing a serious health threat. In this study, we show for the first time that Zika virus employs cell membrane lipid rafts as a portal of entry into Vero cells. We previously demonstrated that the antifungal drug Amphotericin B (AmphB) hampers a microbe-host cell interaction through the disruption of lipid raft architecture. Here, we found that Amphotericin B by the same mechanism of action inhibits both Zika virus cell entry and replication. These data encourage further studies on the off-label use of Amphotericin B in Zika virus infections as a new and alternate antiviral therapy.

Interspecies Isobaric Labeling-Based Quantitative Proteomics Reveals Protein Changes in the Ovary of Aedes aegypti Coinfected With ZIKV and Wolbachia.

Zika is a vector-borne disease caused by an arbovirus (ZIKV) and overwhelmingly transmitted by Ae. aegypti. This disease is linked to adverse fetal outcomes, mostly microcephaly in newborns, and other clinical aspects such as acute febrile illness and neurologic complications, for example, Guillain-Barré syndrome. One of the most promising strategies to mitigate arbovirus transmission involves releasing Ae. aegypti mosquitoes carrying the maternally inherited endosymbiont bacteria Wolbachia pipientis. The presence of Wolbachia is associated with a reduced susceptibility to arboviruses and a fitness cost in mosquito life-history traits such as fecundity and fertility. However, the mechanisms by which Wolbachia influences metabolic pathways leading to differences in egg production remains poorly known. To investigate the impact of coinfections on the reproductive tract of the mosquito, we applied an isobaric labeling-based quantitative proteomic strategy to investigate the influence of Wolbachia wMel and ZIKV infection in Ae. aegypti ovaries. To the best of our knowledge, this is the most complete proteome of Ae. aegypti ovaries reported so far, with a total of 3913 proteins identified, were also able to quantify 1044 Wolbachia proteins in complex sample tissue of Ae. aegypti ovary. Furthermore, from a total of 480 mosquito proteins modulated in our study, we discuss proteins and pathways altered in Ae. aegypti during ZIKV infections, Wolbachia infections, coinfection Wolbachia/ZIKV, and compared with no infection, focusing on immune and reproductive aspects of Ae. aegypti. The modified aspects mainly were related to the immune priming enhancement by Wolbachia presence and the modulation of the Juvenile Hormone pathway caused by both microorganism's infection.

The 2021 Zika outbreak in Uttar Pradesh state of India: Tackling the emerging public health threat.

Zika virus is an RNA virus belonging to the Flavivirus family that is chiefly transmitted by the female Aedes mosquito. The Zika virus first infected humans in Uganda and Tanzania in 1952. Since, it has spread to several parts of the world causing outbreaks of variable extent. In India, these outbreaks have been reported from Gujarat, Tamil Nadu, Madhya Pradesh, Rajasthan, Kerala, and Maharashtra. The most recent outbreak is from the most populous state of India, Uttar Pradesh, where the climate is conducive to the breeding and transmission of other arboviral infections such as Dengue, Chikungunya, and Malaria. These infections also happen to share similar incubation periods and overlapping clinical manifestations with Zika virus (ZIKV) infection, leading to misdiagnoses or delayed diagnosis. We aim to provide an account of the outbreak, its repercussions, errors made in attempting to contain the spread of the disease, and, measures to be taken in the future.

Dengue encephalitis featuring "double-doughnut" sign - A case report.

Introduction: Dengue is a common febrile illness caused by Dengue virus and spread by Aedes mosquitoes. The neurological complications like encephalopathy or encephalitis or immune-mediated neurological syndromes are uncommon though. Discrete neuroimaging findings in this setting are even rarer. We report a case of dengue encephalitis with uncommon MRI features in a young female. Case presentation: The patient presented with complains of fever, vomiting, weakness in all limbs and difficulty in speech. Neurological examination revealed bilateral horizontal gaze palsy with impaired oculo-cephalic reflex, bulbar dysarthria and quadriplegia with bilateral planters up-going. Laboratory reported anemia, thrombocytopenia and positive NS1 antigen while excluding other tropical and immunological diseases. Brain MRI revealed extensive thalamic involvement as unique "double-doughnut" sign along with lesions in brainstem. The patient received supportive treatment in intensive unit and was discharged following improvement in clinical condition and laboratory reports. Clinical discussion: Dengue can infect the central nervous system directly as encephalitis or can have neurological consequences following multi-organ dysfunction and shock as encephalopathy or post-infection immunological syndromes as Guillain-Barré Syndrome or cerebrovascular complications or dengue muscle dysfunction. The MRI appearance of "double-doughnut" sign points towards dengue encephalitis in appropriate setting. Conclusion: A high index of suspicion is required to make a diagnosis of dengue encephalitis. The "double-doughnut" sign in MRI sequences has the potential to become a diagnostic marker for dengue encephalitis.

Pathogenesis and Manifestations of Zika Virus-Associated Ocular Diseases.

Zika virus (ZIKV) is mosquito-borne flavivirus that caused a significant public health concern in French Polynesia and South America. The two major complications that gained the most media attention during the ZIKV outbreak were Guillain-Barré syndrome (GBS) and microcephaly in newborn infants. The two modes of ZIKV transmission are the vector-borne and non-vector borne modes of transmission. Aedes aegypti and Aedes albopictus are the most important vectors of ZIKV. ZIKV binds to surface receptors on permissive cells that support infection and replication, such as neural progenitor cells, dendritic cells, dermal fibroblasts, retinal pigment epithelial cells, endothelial cells, macrophages, epidermal keratinocytes, and trophoblasts to cause infection. The innate immune response to ZIKV infection is mediated by interferons and natural killer cells, whereas the adaptive immune response is mediated by CD8+T cells, Th1 cells, and neutralizing antibodies. The non-structural proteins of ZIKV, such as non-structural protein 5, are involved in the evasion of the host's immune defense mechanisms. Ocular manifestations of ZIKV arise from the virus' ability to cross both the blood-brain barrier and blood-retinal barrier, as well as the blood-aqueous barrier. Most notably, this results in the development of GBS, a rare neurological complication in acute ZIKV infection. This can yield ocular symptoms and signs. Additionally, infants to whom ZIKV is transmitted congenitally develop congenital Zika syndrome (CZS). The ocular manifestations are widely variable, and include nonpurulent conjunctivitis, anterior uveitis, keratitis, trabeculitis, congenital glaucoma, microphthalmia, hypoplastic optic disc, and optic nerve pallor. There are currently no FDA approved therapeutic agents for treating ZIKV infections and, as such, a meticulous ocular examination is an important aspect of the diagnosis. This review utilized several published articles regarding the ocular findings of ZIKV, antiviral immune responses to ZIKV infection, and the pathogenesis of ocular manifestations in individuals with ZIKV infection. This review summarizes the current knowledge on the viral immunology of ZIKV, interactions between ZIKV and the host's immune defense mechanism, pathological mechanisms, as well as anterior and posterior segment findings associated with ZIKV infection.

Natural products as Zika antivirals.

Zika virus (ZIKV) is an arbovirus belonging to the flavivirus genus and is transmitted in Aedes mosquito vectors. Since its discovery in humans in 1952 in Uganda, ZIKV has been responsible for many outbreaks in South America, Africa, and Asia. Patients infected with ZIKV are usually asymptomatic; mild symptoms include fever, joint and muscle pain, and fatigue. However, severe infections may have neurological implications, such as Guillain-Barré syndrome and fetal microcephaly. To date, there are no existing approved therapeutic drugs or vaccines against ZIKV infections; treatments mainly target the symptoms of infection. Preventive measures against mosquito breeding are the main strategy for limiting the spread of the virus. Antiviral drug research for the treatment of ZIKV infection has been rapidly developing, with many drug candidates emerging from drug repurposing studies, and compound screening. In particular, several studies have demonstrated the potential of natural products as antivirals for ZIKV infection. Hence, this paper will review recent advances in natural products in ZIKV antiviral drug discovery.

Neuroimaging features of arboviral infections in the Americas.

Arboviruses are zoonotic RNA viruses maintained in nature in cycles that involve arthropod vectors. The arboviruses that cause disease in humans are members of the Bunyaviridae, Togaviridae, Flaviviridae, and Reoviridae families. These viral species have geographically and climatically restricted distributions due to particular ecological and vector features. The main emerging arboviruses in the Americas are dengue, zika, yellow fever (Flaviviridae), and chikungunya (Togaviridae). All of these viruses can be transmitted by the Aedes aegypti and Aedes albopictus mosquitoes. Although not commonly, these infections are associated with neurological complications, characterized mainly by hemorrhage, encephalitis, myelitis, acute disseminated encephalomyelitis, Guillain-Barré syndrome, and/or congenital malformations. This review describes the imaging features of the neurological complications of these emerging arbovirus infections.

Low Immune Cross-Reactivity between West Nile Virus and a Zika Virus Vaccine Based on Modified Vaccinia Virus Ankara.

Zika virus (ZIKV) is a mosquito-borne flavivirus whose infection in pregnant women is associated with a spectrum of birth defects, which are together referred as Congenital Zika Syndrome. In addition, ZIKV can also induce Guillain-Barré syndrome, which is an autoimmune disease with neurological symptoms. The recent description of the first local infections of ZIKV in the European continent together with the expansion of one of its potential vectors, the Asian tiger mosquito (Aedes albopictus), invite us to be prepared for future outbreaks of ZIKV in this geographical region. However, the antigenic similarities of ZIKV with other flaviviruses can lead to an immune cross-reactivity with other circulating flaviviruses inducing, in some cases, flavivirus-disease exacerbation by antibody-dependent enhancement (ADE) of infection, which is a major concern for ZIKV vaccine development. Until now, West Nile virus (WNV) is the main medically relevant flavivirus circulating in the Mediterranean Basin. Therefore, anticipating the potential scenario of emergency vaccination against ZIKV in areas of Europe where WNV is endemic, in this investigation, we have evaluated the cross-reactivity between WNV and our previously developed ZIKV vaccine candidate based on modified vaccinia virus Ankara (MVA) vector expressing ZIKV structural proteins (MVA-ZIKV). To this end, mice were first immunized with MVA-ZIKV, subsequently challenged with WNV, and then, the ZIKV- and WNV-specific immune responses and protection against WNV were evaluated. Our results indicate low cross-reactivity between the MVA-ZIKV vaccine candidate and WNV and absence of ADE, supporting the safety of this ZIKV vaccine candidate in areas where the circulation of WNV is endemic.