Control Of Zika Virus Infection Research Articles

Control of maternal Zika virus infection during pregnancy is associated with lower antibody titers in a macaque model.

Zika virus (ZIKV) infection during pregnancy results in a spectrum of birth defects and neurodevelopmental deficits in prenatally exposed infants, with no clear understanding of why some pregnancies are more severely affected. Differential control of maternal ZIKV infection may explain the spectrum of adverse outcomes. Here, we investigated whether the magnitude and breadth of the maternal ZIKV-specific antibody response is associated with better virologic control using a rhesus macaque model of prenatal ZIKV infection. We inoculated 18 dams with an Asian-lineage ZIKV isolate (PRVABC59) at 30-45 gestational days. Plasma vRNA and infectious virus kinetics were determined over the course of pregnancy, as well as vRNA burden in the maternal-fetal interface (MFI) at delivery. Binding and neutralizing antibody assays were performed to determine the magnitude of the ZIKV-specific IgM and IgG antibody responses throughout pregnancy, along with peptide microarray assays to define the breadth of linear ZIKV epitopes recognized. Dams with better virologic control (n= 9) cleared detectable infectious virus and vRNA from the plasma by 7 days post-infection (DPI) and had a lower vRNA burden in the MFI at delivery. In comparison, dams with worse virologic control (n= 9) still cleared detectable infectious virus from the plasma by 7 DPI but had vRNA that persisted longer, and had higher vRNA burden in the MFI at delivery. The magnitudes of the ZIKV-specific antibody responses were significantly lower in the dams with better virologic control, suggesting that higher antibody titers are not associated with better control of ZIKV infection. Additionally, the breadth of the ZIKV linear epitopes recognized did not differ between the dams with better and worse control of ZIKV infection. Thus, the magnitude and breadth of the maternal antibody responses do not seem to impact maternal virologic control. This may be because control of maternal infection is determined in the first 7 DPI, when detectable infectious virus is present and before robust antibody responses are generated. However, the presence of higher ZIKV-specific antibody titers in dams with worse virologic control suggests that these could be used as a biomarker of poor maternal control of infection and should be explored further.

The mechanisms underlying the immune control of Zika virus infection at the maternal-fetal interface.

Unlike other Flaviviruses, Zika virus (ZIKV) infection during the first trimester of pregnancy causes severe pregnancy outcomes including the devastating microcephaly and diseases associated with placental dysfunctions. We have previously reported that the maternal decidua basalis, the major maternal-fetal interface, serves as a replication platform enabling virus amplification before dissemination to the fetal compartment. However, the rate of congenital infection is quite low, suggesting the presence of a natural barrier against viral infection. Using primary cells from first-trimester pregnancy samples, we investigated in this study how the maternal decidua can interfere with ZIKV infection. Our study reveals that whether through their interactions with dNK cells, the main immune cell population of the first-trimester decidua, or their production of proinflammatory cytokines, decidual stromal cells (DSCs) are the main regulators of ZIKV infection during pregnancy. We also validate the functional role of AXL as a crucial receptor for ZIKV entry in DSCs and demonstrate that targeted inhibition of ligand-receptor interaction at the early stage of the infection is effective in drastically reducing virus pathogenesis at the maternal-fetal interface. Collectively, our results provide insights into the mechanisms through which ZIKV infection and spreading can be limited. The strategy of circumventing viral entry at the maternal-fetus interface limits virus dissemination to fetal tissues, thereby preventing congenital abnormalities.

Identification of an N-phenylsulfonyl-2-(piperazin-1-yl)methyl-benzonitrile derivative as Zika virus entry inhibitor

Zika virus (ZIKV) infection could cause severe neurological complications such as neonatal microcephaly, Guillain-Barré syndrome, and myelitis in adults. No vaccine or therapeutic drug is available for prevention and control of ZIKV infection yet. Based on previously reported anti-ZIKV hit compound 1, a series of novel N-benzoyl or phenylsulfonyl substituted 2-(piperazin-1-yl)methyl-benzonitrile (PMBN) derivatives was designed, synthesized, and investigated for the antiviral activity against ZIKV replication in different cell-based phenotypic assays. The results indicated that N-phenylsulfonyl-PMBN derivative 24 displayed the comparable antiviral activity and higher oral availability than hit compound 1. Meanwhile, mechanism of action study confirmed that compound 24 acts on the early entry stage of ZIKV life cycle. The identification of this new ZIKV entry inhibitor chemotype provided a promising lead for further optimization to develop new drug for ZIKV infection.

Efficient Control of Zika Virus Infection Induced by a Non-Replicating Adenovector Encoding Zika Virus NS1/NS2 Antigens Fused to the MHC Class II-Associated Invariant Chain.

It is generally believed that a successful Zika virus (ZIKV) vaccine should induce neutralizing antibodies against the ZIKV envelope (E) protein to efficiently halt viral infection. However, E-specific neutralizing antibodies have been implicated in a phenomenon called antibody-dependent enhancement, which represents an ongoing concern in the flavivirus-vaccinology field. In this report, we investigated the vaccination potential of replication-deficient adenoviral vectors encoding the ZIKV non-structural proteins 1 and 2 (NS1/NS2) and employed the strategy of linking the antigens to the MHC-II associated invariant chain (li) to improve immunogenicity and by inference, the level of protection. We demonstrated that li-linkage enhanced the production of anti-NS1 antibodies and induced an accelerated and prolonged polyfunctional CD8 T cell response in mice, which ultimately resulted in a high degree of protection against ZIKV infection of the CNS.

A genetically stable Zika virus vaccine candidate protects mice against virus infection and vertical transmission

Although live attenuated vaccines (LAVs) have been effective in the control of flavivirus infections, to date they have been excluded from Zika virus (ZIKV) vaccine trials due to safety concerns. We have previously reported two ZIKV mutants, each of which has a single substitution in either envelope (E) glycosylation or nonstructural (NS) 4B P36 and displays a modest reduction in mouse neurovirulence and neuroinvasiveness, respectively. Here, we generated a ZIKV mutant, ZE4B-36, which combines mutations in both E glycosylation and NS4B P36. The ZE4B-36 mutant is stable and attenuated in viral replication. Next-generation sequence analysis showed that the attenuating mutations in the E and NS4B proteins are retained during serial cell culture passages. The mutant exhibits a significant reduction in neuroinvasiveness and neurovirulence and low infectivity in mosquitoes. It induces robust ZIKV-specific memory B cell, antibody, and T cell-mediated immune responses in type I interferon receptor (IFNR) deficient mice. ZIKV-specific T cell immunity remains strong months post-vaccination in wild-type C57BL/6 (B6) mice. Vaccination with ZE4B-36 protects mice from ZIKV-induced diseases and vertical transmission. Our results suggest that combination mutations in E glycosylation and NS4B P36 contribute to a candidate LAV with significantly increased safety but retain strong immunogenicity for prevention and control of ZIKV infection.

Recent progresses and remaining challenges for the detection of Zika virus.

Zika virus (ZIKV) has emerged as a particularly notorious mosquito-borne flavivirus, which can lead to a devastating congenital syndrome in the fetuses of pregnant mothers (e.g., microcephaly, spasticity, craniofacial disproportion, miscarriage, and ocular abnormalities) and cause the autoimmune disorder Guillain-Barre' syndrome of adults. Due to its severity and rapid dispersal over several continents, ZIKV has been acknowledged to be a global health concern by the World Health Organization. Unfortunately, the ZIKV has recently resurged in India with the potential for devastating effects. Researchers from all around the world have worked tirelessly to develop effective detection strategies and vaccines for the prevention and control of ZIKV infection. In this review, we comprehensively summarize the most recent research into ZIKV, including the structural biology and evolution, historical overview, pathogenesis, symptoms, and transmission. We then focus on the detection strategies for ZIKV, including viral isolation, serological assays, molecular assays, sensing methods, reverse transcription loop mediated isothermal amplification, transcription-mediated amplification technology, reverse transcription strand invasion based amplification, bioplasmonic paper-based device, and reverse transcription isothermal recombinase polymerase amplification. To conclude, we examine the limitations of currently available strategies for the detection of ZIKV, and outline future opportunities and research challenges.

Primary care nurses’ knowledge on Zika virus infection during pregnancy

Cases related to Zika Virus infections in Brazil have become a severe public health problem due to its relation to microcephaly and other neurological and development problems in newborn babies of mothers who were infected by the Zika virus. Nurses are vital professionals in combating this infection, both for prevention and vector control; as well as handling the target public. Therefore, the research aimed to investigate Primary Care nurses’ knowledge on Zika virus infection during pregnancy. It is a descriptive field study with qualitative approach carried out at Family Health Strategy, in the city of Cajazeiras, Paraíba, Brazil. Semi-structured interviews were conducted for data collection, which were submitted to thematic-content analysis. The nurses replied that there is not much information about Zika virus infections, and reported brain impairment as the main consequence for the newborn baby. Nurses also revealed that many women of the community showed negative feelings towards the pregnancy, and they pointed out the importance of health education actions in the community for dissemination of information on Zika virus infection control and prevention. Nurses’ contribution regarding the assistance provided to the community is considered satisfactory. However, there was a need to bring efficient and updated professional training to the reality of each community. Therefore, it is suggested that training be provided through continued health education to professionals.

Emergence of Zika Virus in Culex tritaeniorhynchus and Anopheles sinensis Mosquitoes in China.

Zika virus (ZIKV) has been isolated from mosquitoes such as Aedes, Mansonia uniformis, and Culex perfuscus; However, the isolation of ZIKV from Anopheles sinensis and Culex tritaeniorhynchus has not yet been reported. In June and July 2018, 22,985 mosquitoes and 57,500 midges were collected in Jiangxi Province in southeastern China. Among them, six strains of ZIKV were isolated from mosquitoes: four from An. sinensis and two from Cx. tritaeniorhynchus. Molecular genetic analysis showed that the ZIKV isolated from An. sinensis and Cx. tritaeniorhynchus belonged to genotype 2 in the Asian evolutionary branch of ZIKV. In addition, the ZIKV strains isolated from An. sinensis and Cx. tritaeniorhynchus had amino acid substitutions identical to ZIKV strains prevalent in South America since 2015. This study is the first to isolate ZIKV from mosquito specimens collected in the wild of Jiangxi Province, China; This is also the first time that ZIKV has been isolated from An. sinensis and Cx. tritaeniorhynchus. Given that An. sinensis and Cx. tritaeniorhynchus have a very wide geographical distribution in China and even in eastern and southern Asia, the isolation of several strains of ZIKV from these two mosquitoes poses new challenges for the prevention and control of ZIKV infection in the mainland of China and countries and regions with the same distribution of mosquitoes.

Prevalence of Zika virus neutralizing antibodies in healthy adults in Vietnam during and after the Zika virus epidemic season: a longitudinal population-based survey

BackgroundBetween 2016 and 2019, 265 cases of Zika virus (ZIKV) infection were reported in Vietnam, predominantly in southern Vietnam. In 2016, a case of ZIKV-associated microcephaly was confirmed in the Central Highlands, and several members of the infant’s family were confirmed to be infected with ZIKV. The study aims to determine the level of immunity to ZIKV in the general population of the ZIKV epidemic region.MethodsA total of 879 serum samples were collected from 801 participants between January 2017 and July 2018, during and after the ZIKV epidemic in Vietnam. The samples were tested for anti-ZIKV immunoglobulin M (IgM) and immunoglobulin G (IgG), and anti-dengue virus (DENV) IgG antibodies using enzyme-linked immunosorbent assays (ELISA). Plaque-reduction neutralization test (PRNT) for ZIKV was performed on all samples, and for DENV on the samples that ZIKV neutralizing antibody positive.ResultsA total of 83 (10.3%) participants had anti-ZIKV IgM. Of the 83, 6 were confirmed to be ZIKV antibodies positive using PRNT and anti-ZIKV IgG ELISA. Of the 718 participants who were anti-ZIKV IgM negative, a further 3 cases were confirmed as positive for antibodies against ZIKV. Of the 9 participants with ZIKV infection, 5 lived in the same village as the infant with ZIKV-associated microcephaly and the other 4 lived in 2 neighboring communes. Repeat samples were collected from the 83 ZIKV IgM positive participants 1.5 years after the first collection. No new cases of ZIKV infection were detected. In addition, 2 of 3 participants with anti-ZIKV NS1 IgG demonstrated a 4- to 8-fold increase in ZIKV neutralizing antibody titer.ConclusionsZIKV was present in the area around Krong Buk, with the rate of ZIKV-specific antibodies was 1.1% in the community since at least 2016. While the low levels of circulation together with low seroprevalence suggests a limited outbreak in the region, the results also reflect on low levels of protective immunity to Zika within the population. These results provide a better understanding of the current ZIKV epidemic status in the region and demonstrate a need for implementation of more effective ZIKV infection control measures.

Experimental infection and vector competence of Zika virus in Aedes aegypti mosquitoes from Acapulco, Guerrero, Mexico.

To gain a better understanding of the Zika virus (ZIKV) vector transmission in Mexico, we determined the vector competence of a local population of Ae. aegypti (Acapulco, Guerrero) for a strain of ZIKV isolated from a Mexican febrile patient. Eggs were hatched and larvae were reared under controlled conditions. After five days post-emergence, female mosquitoes were fed an infectious blood-meal containing ZIKV. Mosquitoes were analyzed at 4, 7 and 14-day post-infection (dpi). Infection (gut), dissemination (wings, legs and heads) and potential transmission (salivary glands) were assessed by RT-qPCR. The Rockefeller Ae. aegypti strain was used as ZIKV infection control. ZIKV infection, dissemination, and potential transmission rates were 96.2, 96.1 and 93.2%, respectively. Ae. aegypti (F1) from Acapulco were very susceptible to ZIKV infection, and showed similar vector competence to that of the susceptible Rockefeller strain. To our knowledge, this is the first report of vector competence for ZIKV performed in a Mexican laboratory.

Progress in serological detection of Zika virus infection

Zika virus (ZIKV) infection may lead to some serious potential complications, such as neonatal microcephaly and Guillain-Barre syndrome. ZIKV epidemics have caused public panic and aroused global concern. World Health Organization (WHO) has listed ZIKV infection as one of the public health emergencies of international concern. This paper focused on the progress in ZIKV detection methods, especially in serological tests, and summarized the advantages and disadvantages of each method in practical application, aiming to provide technical reference for the prevention and control of Zika virus infection. Key words: Zika virus; Serological detection; Antibody; Antigen

Monocytes and macrophages limit systemic infection and modulate the CD4 T cell response during Zika virus infection in mice

Abstract Monocytes and macrophages are antiviral innate immune effector cells that also serve as cellular hosts of Zika virus (ZIKV). To investigate the precise role of monocytes and macrophages during ZIKV infection in vivo, monocytes and macrophages were depleted with clodronate liposomes before ZIKV infection in wild-type C57BL/6 mice, and viral burden and ZIKV-specific immune responses were assessed. Chlodronate liposometreated mice had higher level of ZIKV RNA in the serum and spleen relative to control liposome-treated mice at early time points after infection. At later time points after infection, chlodronate liposome-treated mice developed an impaired ZIKV-specific Th1 response in terms of both magnitude and quality, whereas they exhibited enhanced Tfh, germinal center B cell, plasma cell, and neutralizing antibody responses as compared to control liposome-treated mice. These data indicate that monocytes and macrophages limit ZIKV dissemination and regulate the balance between Th1 versus Tfh responses during ZIKV infection. Thus, monocytes and macrophages contribute to both the innate control of ZIKV infection and regulation of the adoptive immune response.

Inhibition of Zika Virus Replication by Silvestrol.

The Zika virus (ZIKV) outbreak in 2016 in South America with specific pathogenic outcomes highlighted the need for new antiviral substances with broad-spectrum activities to react quickly to unexpected outbreaks of emerging viral pathogens. Very recently, the natural compound silvestrol isolated from the plant Aglaia foveolata was found to have very potent antiviral effects against the (−)-strand RNA-virus Ebola virus as well as against Corona- and Picornaviruses with a (+)-strand RNA-genome. This antiviral activity is based on the impaired translation of viral RNA by the inhibition of the DEAD-box RNA helicase eukaryotic initiation factor-4A (eIF4A) which is required to unwind structured 5´-untranslated regions (5′-UTRs) of several proto-oncogenes and thereby facilitate their translation. Zika virus is a flavivirus with a positive-stranded RNA-genome harboring a 5′-capped UTR with distinct secondary structure elements. Therefore, we investigated the effects of silvestrol on ZIKV replication in A549 cells and primary human hepatocytes. Two different ZIKV strains were used. In both infected A549 cells and primary human hepatocytes, silvestrol has the potential to exert a significant inhibition of ZIKV replication for both analyzed strains, even though the ancestor strain from Uganda is less sensitive to silvestrol. Our data might contribute to identify host factors involved in the control of ZIKV infection and help to develop antiviral concepts that can be used to treat a variety of viral infections without the risk of resistances because a host protein is targeted.

Structures of Zika Virus E & NS1: Relations with Virus Infection and Host Immune Responses.

Zika virus (ZIKV), first discovered in the Zika forest in Uganda in 1947 was understudied until the recent explosive epidemic in several South American countries where it has become strongly associated with congenital birth defects leading to severe cranial malformations and neurological conditions. The increase in number of case of microcephaly in newborn children associated with ZIKV infection triggered the World Health Organization to declare the epidemic as a Public Health Emergency of International Concern in February of 2016. ZIKV is a member of the flavivirus genus and is transmitted by Aedes aegypti mosquitoes, however in the current epidemic clear evidence is emerging to suggest the virus can be sexually transmitted from human to human. The differences in epidemiology and manifestations of ZIKV infection during these outbreaks have prompted researchers to investigate mechanisms of dissemination, pathogenesis, and host immune response which contributes significantly to the control of the virus infection. The E and NS1 proteins of ZIKV are the major targets for neutralizing and protective antibodies. In this chapter, we mainly focus on recent research on the crystal structures of the ZIKV E and NS1 proteins, and their relations with virus infection and immune responses. These studies will be helpful to develop novel therapeutics and vaccines for protection and control of ZIKV infection.

Viperin is an important host restriction factor in control of Zika virus infection

Zika virus (ZIKV) infection has emerged as a global health threat and infection of pregnant women causes intrauterine growth restriction, spontaneous abortion and microcephaly in newborns. Here we show using biologically relevant cells of neural and placental origin that following ZIKV infection, there is attenuation of the cellular innate response characterised by reduced expression of IFN-β and associated interferon stimulated genes (ISGs). One such ISG is viperin that has well documented antiviral activity against a wide range of viruses. Expression of viperin in cultured cells resulted in significant impairment of ZIKV replication, while MEFs derived from CRISPR/Cas9 derived viperin−/− mice replicated ZIKV to higher titers compared to their WT counterparts. These results suggest that ZIKV can attenuate ISG expression to avoid the cellular antiviral innate response, thus allowing the virus to replicate unchecked. Moreover, we have identified that the ISG viperin has significant anti-ZIKV activity. Further understanding of how ZIKV perturbs the ISG response and the molecular mechanisms utilised by viperin to suppress ZIKV replication will aid in our understanding of ZIKV biology, pathogenesis and possible design of novel antiviral strategies.

Optimal control of Zika virus infection by vector elimination, vector-to-human and human-to-human contact reduction

The recent outbreak of mosquito-borne Zika virus (ZIKV) in Brazil, with estimated cases surpassing 1.5 million, has gained attention due to its rapid spread and neurological complications associated with the infection such as microcephaly and Guillain-Barré syndrome. Beside vector transmission, primarily via Aedes mosquitoes, sexual transmission also contributes to the virus outbreak. The epidemiological patterns of these viruses suggest that Zika virus could cause other outbreaks, particularly in tropical regions with high vector concentration. To plan and prepare for a counter-control measure, it is important to study the previous cases. Hence, the control model is proposed from the deterministic model of Zika virus infection. Regarding control measures, the control functions for these strategies; vector elimination, vector-to-human contact reduction, and human-to-human contact reduction are introduced into the system. The necessary conditions for the optimal controls are determined using Pontryagin’s maximum principle and the optimality system is solved using Rung-Kutta fourth order scheme. Consequently, numerical results of the system with control and the system without control are shown and discussed.

Adaptive Immune Responses to Zika Virus Are Important for Controlling Virus Infection and Preventing Infection in Brain and Testes.

The recent association between Zika virus (ZIKV) and neurologic complications, including Guillain-Barré syndrome in adults and CNS abnormalities in fetuses, highlights the importance in understanding the immunological mechanisms controlling this emerging infection. Studies have indicated that ZIKV evades the human type I IFN response, suggesting a role for the adaptive immune response in resolving infection. However, the inability of ZIKV to antagonize the mouse IFN response renders the virus highly susceptible to circulating IFN in murine models. Thus, as we show in this article, although wild-type C57BL/6 mice mount cell-mediated and humoral adaptive immune responses to ZIKV, these responses were not required to prevent disease. However, when the type I IFN response of mice was suppressed, then the adaptive immune responses became critical. For example, when type I IFN signaling was blocked by Abs in Rag1-/- mice, the mice showed dramatic weight loss and ZIKV infection in the brain and testes. This phenotype was not observed in Ig-treated Rag1-/- mice or wild-type mice treated with anti-type I IFNR alone. Furthermore, we found that the CD8+ T cell responses of pregnant mice to ZIKV infection were diminished compared with nonpregnant mice. It is possible that diminished cell-mediated immunity during pregnancy could increase virus spread to the fetus. These results demonstrate an important role for the adaptive immune response in the control of ZIKV infection and imply that vaccination may prevent ZIKV-related disease, particularly when the type I IFN response is suppressed as it is in humans.

Adaptive immune responses to Zika virus are important for controlling virus infection and preventing infection in brain and testes

Abstract The recent association between Zika virus (ZIKV) and neurological complications including Guillain-Barré Syndrome (GBS) in adults and CNS abnormalities in fetuses highlights the urgency to understand the immunological mechanisms controlling this emerging infection. Studies have indicated that ZIKV evades the human type I IFN response suggesting a role for the adaptive immune response in resolving infection. However, the inability of ZIKV to antagonize the mouse IFN response renders the virus highly susceptible to circulating IFN in murine models. Thus, as we show here, although wild type C57BL/6 mice mount both cell-mediated and humoral adaptive immune responses to ZIKV, these responses were not required to prevent disease. However, when the type I IFN response of mice was suppressed, then the adaptive immune responses became critical. For example, when type I IFN signaling was blocked by antibodies in Rag1−/− immunodeficient mice, the mice showed dramatic weight loss and ZIKV infection in the brain and testes. This phenotype was not observed in Rag1−/− mice or mice treated with anti-IFNAR alone. Furthermore, we found that the CD8+ T cell responses of pregnant mice to ZIKV infection were diminished compared to non-pregnant mice. It is possible that diminished cell-mediated immunity during pregnancy could increase virus spread to the fetus. These results demonstrate an important role for the adaptive immune response in control of ZIKV infection, and imply that vaccination may prevent ZIKV-related disease, particularly when the type I IFN response is suppressed as it is in humans.

T cell infiltration associated with neurodegeneration and Zika virus control in the CNS of immunocompetent, neonatal mice.

Abstract The recent spread of Zika virus (ZIKV) and its association with neurological disorders as well as congenital defects has created an urgent need to develop animal models that allow the elucidation of pathogenesis following ZIKV infection and to develop and test therapeutic agents that will prevent or eliminate CNS disease. We have developed a novel model of ZIKV infection in mice, using B6 WT, neonatal mice that are susceptible to contemporary ZIKV (PRVABC59) CNS infection following peripheral, subcutaneous inoculation at P1. Immunocompetent B6 WT mice develop a discrete neurological disease that includes: unsteady gait, kinetic tremors, severe ataxia and seizures by 12–15 dpi that gradually resolve. Gene expression and immunohistochemistry demonstrate inflammation in the CNS of ZIKV infected B6 WT mice starting after 9 dpi and infiltration of immune cells into the parenchyma of the CNS beginning concomitantly. At the peak of disease (15 dpi), immune cell infiltrates in the CNS consisted primarily of T cells, particularly CD8+ T cells. Gene expression analysis indicated an upregulation of genes consistent with this infiltration. Immunohistochemistry of the CNS indicates a concomitant increase in apoptosis and neurodegeneration after 9 dpi in the CNS particularly in the granular and Purkinje cell layers of the cerebellum. The role of T cells in the control of ZIKV infection in the CNS and the periphery will be explored.

Zika Virus: Transmission, Detection, Control, and Prevention.

Zika virus (ZIKV) is a mosquito-borne Flavivirus discovered in Uganda in the 1940s. To date, three major ZIKV outbreaks have been reported. ZIKV infections have known to be primarily asymptomatic while causing mild illness in a few cases. However, the recent emergence and spread of ZIKV in the Americas has resulted in the declaration of “Public Health Emergency of International Concern” due to the potential association between the infection and prenatal microcephaly or other brain anomalies. In Brazil, a 20-fold increase in prenatal microcephaly cases and 19% increase in Guillain-Barré Syndrome (GBS) cases were reported in 2015, as compared to the preceding year. The probable deleterious effects of ZIKV infection prompt the urgent development of diagnostics and therapeutics. To this end, the existing evidences supporting the increasingly common prenatal microcephaly and GBS association and the current known ZIKV transmission dynamics, modes of detection (molecular and serology-based), and current control strategies are summarized in this review. This review also emphasizes the importance of understanding ZIKV transmission in order to design a sensitive yet cost and time-efficient detection technique. Development of an efficient detection technique would subsequently allow for better surveillance and control of ZIKV infection. Currently, limited literature is available on the pathogenesis of ZIKV, hence, focusing on the modes of ZIKV transmission could potentially contribute to the understanding of the disease spectrum and formulation of targeted treatment and control.