Spread Of Zika Virus Research Articles

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.

A cathelicidin antimicrobial peptide from Hydrophis cyanocinctus inhibits Zika virus infection by downregulating expression of a viral entry factor

Zika virus (ZIKV) is a re-emerging flavivirus that causes conditions such as microcephaly and testis damage. The spread of ZIKV has become a major public health concern. Recent studies indicated that antimicrobial peptides are an ideal source for screening antiviral candidates with broad-spectrum antiviral activities, including against ZIKV. We herein found that Hc-CATH, a cathelicidin antimicrobial peptide identified from the sea snake Hydrophis cyanocinctus in our previous work, conferred protection against ZIKV infection in host cells and showed preventative efficacy and therapeutic efficacy in C57BL/6J mice, Ifnar1−/− mice, and pregnant mice. Intriguingly, we revealed that Hc-CATH decreased the susceptibility of host cells to ZIKV by downregulating expression of AXL, a TAM (TYRO3, AXL and MERTK) family kinase receptor that mediates ZIKV infection, and subsequently reversed the negative regulation of AXL on host’s type I interferon response. Furthermore, we showed that the cyclo-oxygenase-2/prostaglandin E2/adenylyl cyclase/protein kinase A pathway was involved in Hc-CATH-mediated AXL downregulation, and Hc-CATH in addition directly inactivated ZIKV particles by disrupting viral membrane. Finally, while we found Hc-CATH did not act on the late stage of ZIKV infection, structure–function relationship studies revealed that α-helix and phenylalanine residues are key structural requirements for its protective efficacy against initial ZIKV infection. In summary, we demonstrate that Hc-CATH provides prophylactic and therapeutic efficacy against ZIKV infection via downregulation of AXL, as well as inactivating the virion. Our findings reveal a novel mechanism of cathelicidin against viral infection and highlight the potential of Hc-CATH to prevent and treat ZIKV infection.

Disputas epistemológicas na associação causal entre Zika vírus e síndrome congênita: uma análise de controvérsia

Abstract An increase in child malformations in 2015 in Brazil is associated with a Zika virus spread months earlier, leaving disputes that still echo. Using elements from a sociology field dedicated to scientific controversy mapping, the present study conducted 15 semi-structured interviews with researchers and administrators involved in this causal association. Our work investigated how actors from different areas observe the role of social conditions in the outcome of the Congenital Zika Syndrome (SCZ) and the paths taken to mitigate them after the epidemic. Concern with social variables and their relevance in the SCZ outcome was observed, with a widespread disappointment about the referral of these issues after the case’s peak; however, these factors have not entered the core narrative about causality. There are epistemic disputes about this outcome. Some attach responsibility to the public power or resign themselves to the result; others demand more active positions from researchers who had access to the decision-making process, with disagreements about the positioning of science. The article points out the need for reflective sciences that dialogue with their agency on the phenomena, as well as for interdisciplinary and multicausal articulations for public narratives on public health crises in Brazil.

Epistemological disputes in the causal link between Zika virus and congenital syndrome: a controversy analysis.

An increase in child malformations in 2015 in Brazil is associated with a Zika virus spread months earlier, leaving disputes that still echo. Using elements from a sociology field dedicated to scientific controversy mapping, the present study conducted 15 semi-structured interviews with researchers and administrators involved in this causal association. Our work investigated how actors from different areas observe the role of social conditions in the outcome of the Congenital Zika Syndrome (SCZ) and the paths taken to mitigate them after the epidemic. Concern with social variables and their relevance in the SCZ outcome was observed, with a widespread disappointment about the referral of these issues after the case's peak; however, these factors have not entered the core narrative about causality. There are epistemic disputes about this outcome. Some attach responsibility to the public power or resign themselves to the result; others demand more active positions from researchers who had access to the decision-making process, with disagreements about the positioning of science. The article points out the need for reflective sciences that dialogue with their agency on the phenomena, as well as for interdisciplinary and multicausal articulations for public narratives on public health crises in Brazil.

Development and characterization of an inducible assay system to measure Zika virus capsid interactions.

The global spread of the mosquito-borne Zika virus (ZIKV) infection and its complications including Guillain-Barré syndrome and fetus microcephaly in 2015 have made ZIKV as a significant public health threat. The capsid protein plays crucial roles in ZIKV replication and thus represents an attractive therapeutic target. However, inhibitors of ZIKV capsid assembly have not been rigorously identified due to the lack of a target-based screening system. In this study, we developed a novel ZIKV capsid interaction method based on a split-luciferase complementation assay, which can be used to measure and quantify ZIKV capsid-capsid (C-C) interaction by the restored luciferase signal when capsid proteins interact with each other. Furthermore, a Tet-on inducible stable cell line was generated to screen inhibitors of capsid dimerization. By using of this system, peptides (Pep.15-24 in the N-terminal region of ZIKV capsid protein and Pep.44-58 in the α2 helix of ZIKV capsid protein) were identified to inhibit ZIKV C-C interaction. Overall, this study developed a novel inducible assay system to measure ZIKV capsid interaction and identify ZIKV capsid multimerization inhibitors, which will be applied for future discovery of ZIKV assembly inhibitors.

Comparing sources of mobility for modelling the epidemic spread of Zika virus in Colombia.

Timely, accurate, and comparative data on human mobility is of paramount importance for epidemic preparedness and response, but generally not available or easily accessible. Mobile phone metadata, typically in the form of Call Detail Records (CDRs), represents a powerful source of information on human movements at an unprecedented scale. In this work, we investigate the potential benefits of harnessing aggregated CDR-derived mobility to predict the 2015-2016 Zika virus (ZIKV) outbreak in Colombia, when compared to other traditional data sources. To simulate the spread of ZIKV at sub-national level in Colombia, we employ a stochastic metapopulation epidemic model for vector-borne diseases. Our model integrates detailed data on the key drivers of ZIKV spread, including the spatial heterogeneity of the mosquito abundance, and the exposure of the population to the virus due to environmental and socio-economic factors. Given the same modelling settings (i.e. initial conditions and epidemiological parameters), we perform in-silico simulations for each mobility network and assess their ability in reproducing the local outbreak as reported by the official surveillance data. We assess the performance of our epidemic modelling approach in capturing the ZIKV outbreak both nationally and sub-nationally. Our model estimates are strongly correlated with the surveillance data at the country level (Pearson's r = 0.92 for the CDR-informed network). Moreover, we found strong performance of the model estimates generated by the CDR-informed mobility networks in reproducing the local outbreak observed at the sub-national level. Compared to the CDR-informed networks, the performance of the other mobility networks is either comparatively similar or substantially lower, with no added value in predicting the local epidemic. This suggests that mobile phone data captures a better picture of human mobility patterns. This work contributes to the ongoing discussion on the value of aggregated mobility estimates from CDRs data that, with appropriate data protection and privacy safeguards, can be used for social impact applications and humanitarian action.

Approximate Solution of the Fractional Order Sterile Insect Technology Model via the Laplace–Adomian Decomposition Method for the Spread of Zika Virus Disease

Sterile insect technology (SIT) is an environmental-friendly method which depends on the release of sterile male mosquitoes that compete with the wild male mosquitoes and mate with wild female mosquitoes, which leads to the production of no offspring and as such reduces the population of Zika virus vector population over time, thereby eliminating the spread of Zika virus in a population. The fractional order sterile insect technology (SIT) model to reduce the spread of Zika virus disease is considered in this present work. We employed the use Laplace–Adomian decomposition method (LADM) to determine an analytical (approximate) solution of the model. The Laplace–Adomian decomposition method (LADM) produced a solution in form of an infinite series that further converges to the exact value. We compared solutions of the fractional model with the classical case using our plots and discovered that the fractional order has more degree of freedom and as such the system can be varied to get many preferred responses of the different classes of the model as the fraction (β) could be varied to the desired rate, say 0.7, 0.4, etc. We have been able to show that LADM can be used to solve an SIT model which has never been done before in literature.

Human Neutrophils Present Mild Activation by Zika Virus But Reduce the Infection of Susceptible Cells.

The emergence of the Zika virus (ZIKV) has highlighted the need for a deeper understanding of virus-host interactions in order to pave the way for the development of antiviral therapies. The present work aimed to address the response of neutrophils during ZIKV infection. Neutrophils are important effector cells in innate immunity implicated in the host’s response to neurotropic arboviruses. Our results indicate that human neutrophils were not permissive to Asian or African ZIKV strain replication. In fact, after stimulation with ZIKV, neutrophils were mild primed against the virus as evaluated through CD11b and CD62L modulation, secretion of inflammatory cytokines and granule content, production of reactive oxygen species, and neutrophil extracellular traps formation. Overall, neutrophils did not affect ZIKV infectivity. Moreover, in vitro ZIKV infection of primary innate immune cells did not trigger neutrophil migration. However, neutrophils co-cultured with ZIKV susceptible cell lineages resulted in lower cell infection frequencies, possibly due to cell-to-cell contact. In vivo, neutrophil depletion in immunocompetent mice did not affect ZIKV spreading to the draining lymph nodes. The data suggest that human neutrophils do not play an antiviral role against ZIKV per se, but these cells might participate in an infected environment shaping the ZIKV infection in other target cells.

Our issue or their issue? Media coverage and framing of the Zika virus epidemic.

How does the news media respond to health emergencies abroad? Between 2015 and 2018, Zika virus spread rapidly throughout Latin America before arriving in the continental United States. Despite the risks to adults and newborns, it is unclear how media coverage developed and framed the threat for its audience. In this paper, we argue that while the frequency of coverage was responsive to infections, its content failed to promote proactive health behaviour. To assess these claims, we analyse each of 442 articles dealing with Zika virus published by The New York Times from 2015-18. We find that the amount of coverage reflected infections but did not change once the disease emerged in the US. Furthermore, content analysis using Linguistic Inquiry and Word Count software reveals that coverage emphasised differences between communities (those affected and those at home) and that present and past time orientations dominated coverage as opposed to future time orientations.

Genome-wide diversity of Zika virus: Exploring spatio-temporal dynamics to guide a new nomenclature proposal.

The Zika virus (ZIKV) disease caused a public health emergency of international concern that started in February 2016. The overall number of ZIKV-related cases increased until November 2016, after which it declined sharply. While the evaluation of the potential risk and impact of future arbovirus epidemics remains challenging, intensified surveillance efforts along with a scale-up of ZIKV whole-genome sequencing provide an opportunity to understand the patterns of genetic diversity, evolution, and spread of ZIKV. However, a classification system that reflects the true extent of ZIKV genetic variation is lacking. Our objective was to characterize ZIKV genetic diversity and phylodynamics, identify genomic footprints of differentiation patterns, and propose a dynamic classification system that reflects its divergence levels. We analysed a curated dataset of 762 publicly available sequences spanning the full-length coding region of ZIKV from across its geographical span and collected between 1947 and 2021. The definition of genetic groups was based on comprehensive evolutionary dynamics analyses, which included recombination and phylogenetic analyses, within- and between-group pairwise genetic distances comparison, detection of selective pressure, and clustering analyses. Evidence for potential recombination events was detected in a few sequences. However, we argue that these events are likely due to sequencing errors as proposed in previous studies. There was evidence of strong purifying selection, widespread across the genome, as also detected for other arboviruses. A total of 50 sites showed evidence of positive selection, and for a few of these sites, there was amino acid (AA) differentiation between genetic clusters. Two main genetic clusters were defined, ZA and ZB, which correspond to the already characterized ‘African’ and ‘Asian’ genotypes, respectively. Within ZB, two subgroups, ZB.1 and ZB.2, represent the Asiatic and the American (and Oceania) lineages, respectively. ZB.1 is further subdivided into ZB.1.0 (a basal Malaysia sequence sampled in the 1960s and a recent Indian sequence), ZB.1.1 (South-Eastern Asia, Southern Asia, and Micronesia sequences), and ZB.1.2 (very similar sequences from the outbreak in Singapore). ZB.2 is subdivided into ZB.2.0 (basal American sequences and the sequences from French Polynesia, the putative origin of South America introduction), ZB.2.1 (Central America), and ZB.2.2 (Caribbean and North America). This classification system does not use geographical references and is flexible to accommodate potential future lineages. It will be a helpful tool for studies that involve analyses of ZIKV genomic variation and its association with pathogenicity and serve as a starting point for the public health surveillance and response to on-going and future epidemics and to outbreaks that lead to the emergence of new variants.

Assessing the risk of spread of Zika virus under current and future climate scenarios

Zika virus (ZIKV) may cause severe microcephaly in newborn babies and Guillain-Barré syndrome in some adults. In recent decades, its range has expanded in 86 countries. There are two ecologically and evolutionarily district cycles: urban cycle and sylvatic cycle. This work aimed to estimate the urban and sylvatic cycle areas of ZIKV throughout the world. The occurrence records of vectors, non-human primate hosts, and ZIKV were collected. We chose historical climate data, predicted vectors distribution, human population density, and elevation data as the variables to fit the maximum entropy model (MaxEnt). Current risk area and future prediction were performed with global climate models (GCMs) and shared socioeconomic pathways (SSPs). Predicting the ZIKV risk area would help tailor related control strategies. The results indicated that 16.6% of the world’s landmass (except Antarctica) is a risk area in the urban cycle. Approximately 6.22 billion people (78.69% of the global population) live in the risk area, with the vast majority in South Asia, tropical Africa, South America, North America, and countries around the Mediterranean Sea. Future climate change decreases the risk area of ZIKV. This study also suggested that the sylvatic cycle happened between the Tropic of Cancer and the Tropic of Capricorn. The overlap region of the urban and sylvatic cycles could be hotpots that ZIKV spill from the sylvatic to the urban cycle. It is indicated that long-term passenger screening, mosquito surveillance, and control are necessary.

Human Polymorphonuclear Cells Support Zika Virus to Cross Endothelial Monolayer and Access Bloodstream

The rapid spread of new outbreaks of human infection caused by Zika virus (ZIKV) has raised many global concerns since 2016. Despite the increasing knowledge of this virus, data on the pathogenesis of ZIKV are still missing. In particular, it is still unknown how the virus crosses the endothelial monolayer and gets access to the bloodstream. In the present work, we used human umbilical vein endothelial cells (HUVECs) as a model to study ZIKV infection in vitro. We demonstrated that HUVECs are an optimal reservoir for viral replication, as they were able to sustain ZIKV infection up to two weeks, without showing a cytopathic effect. In order to evaluate the integrity of endothelial monolayer, immunofluorescence was performed on mock-infected or ZIKV-infected cells ± peripheral blood mononuclear cells (PBMCs) or polymorphonuclear cells (PMN), 48 h p.i., by using an anti-VE-Cadherin antibody, a major adherence protein that maintains the integrity of intercellular junctions. In addition to infection, we noted that the presence of some components of the immune system, such as PMNs, played an important role in altering the endothelial monolayer in cell junctions, suggesting that presence at the site of infection probably promotes the spread of ZIKV in vivo in the bloodstream.

Seroprevalence of Zika Virus in Amphawa District, Thailand, after the 2016 Pandemic

In 2016, Zika virus (ZIKV) infection was declared a public health emergency of international concern because of the neurological consequences in babies born to infected people. Because of the mild and nonspecific symptoms, serological tests are essential in epidemiological studies. However, cross-reactive antibodies between other Flaviviridae members may complicate the interpretation of results of these tests. This study investigated the seroprevalence of ZIKV infection in Samut Songkhram in central Thailand which was affected by the Zika outbreak of 2016. Three hundred and fifty volunteers aged 5–50 years in Amphawa District, Samut Songkhram, were enrolled between April 2017 and April 2018. ZIKV nonstructural protein 1 (NS1) immunoglobulin G enzyme-linked immunosorbent assay (ELISA) was used to screen serum samples collected on the first day of enrollment and after 6 and 12 months. The seroprevalence and seroconversion of ZIKV were assessed. Cases of ZIKV seroconversion were verified as evidence of ZIKV infection by NS1 blockade-of-binding ELISA and plaque reduction neutralization test (PRNT50). ZIKV seroprevalence in Amphawa was 15.1–17.8% with no significant change over the year. The total seroconversion rate throughout the year was 7/100 person-years. The ratio of asymptomatic to symptomatic infections was 4.5:1. The cases in our study confirmed the occurrence of occult ZIKV infections in the community. These undetected infections might promote the spread of ZIKV in vulnerable groups of the community.

Zika Virus Immunoglobulin G Seroprevalence among Young Adults Living with HIV or without HIV in Thailand from 1997 to 2017.

Zika virus (ZIKV) epidemiological data in Thailand are limited. We assessed ZIKV IgG seroprevalence among young adults during 1997–2017 and determined factors associated with ZIKV IgG seropositivity. This retrospective laboratory study included randomly selected subjects aged 18–25 years participating in large clinical studies conducted in Thailand during 1997–2017. Stored plasma samples were analyzed for ZIKV IgG using an ELISA test (Anti-Zika Virus IgG, EUROIMMUN, Lübeck, Germany). Sociodemographic, clinical and laboratory data were used in univariable and multivariable analyses to identify factors associated with ZIKV IgG positivity. Of the 1648 subjects included, 1259 were pregnant women, 844 were living with HIV and 111 were living with HBV. ZIKV IgG seroprevalence was similar among the HIV-infected and -uninfected pregnant women (22.8% vs. 25.8%, p-value = 0.335) and was overall stable among the pregnant women, with a 25.2% prevalence. Factors independently associated with ZIKV IgG positivity included an age of 23–25 years as compared to 18–20 years, an HIV RNA load below 3.88 log10 copies/mL and birth in regions outside northern Thailand. Our study shows that a large proportion of the population in Thailand probably remains susceptible to ZIKV infection, which could be the ground for future outbreaks. Continued surveillance of ZIKV spread in Thailand is needed to inform public health policies.

An Efficient Computational Method of Motif Finding in the Zika Virus Genome

The Zika virus (ZIKV) outbreak and spread is a global health emergency declared by World Health Organization. ZIKV rapidly spread across the world, causing neurological disorders. It is gaining public and scientific consideration. ZIKV genome biology and molecular structure are better understood with published papers. Genetic regulation is better understood by finding the motif in the DNA Genome sequence. The transcription factor binding sites need to be identified to understand the genetic code. There is diversity in gene expression. Motif-finding methods work towards efficiently identifying the repeated patterns in the genome. ZIKV genome sequence is used in the study. Identifying the motif is still a difficult task. There is a low probability of identifying the binding sites. Finding all possible solutions is challenging as it requires a lot of time and has high space complexity for finding long motifs. The Greedy search technique with pseudocount finds the motif in real-time. The count matrix is computed, and the profile matrix is constructed from the genome of the Zika virus. The calculated consensus string helps in calculating the score of the motif. The Greedy motif search technique is applied in this paper to find the motifs in the Zika virus Genome. This technique is not applied earlier to find the motifs in Zika Virus. The motifs are identified using a Greedy motif search without pseudocount and with pseudocount.

Flavivirus replication kinetics in early-term placental cell lines with different differentiation pathways

BackgroundThe uncontrollable spread of Zika virus (ZIKV) in the Americas during 2015–2017, and its causal link to microcephaly in newborns and Guillain-Barré syndrome in adults, led the World Health Organisation to declare it a global public health emergency. One of the most notable features of ZIKV pathogenesis was the ability of the virus to pass the placental barrier to infect the growing foetus. This pathogenic trait had not been observed previously for medically important flaviviruses, including dengue and yellow fever viruses.MethodsIn this study we evaluated the replication kinetics of ZIKV and the related encephalitic flavivirus West Nile strain Kunjin virus (WNVKUN) in early-term placental cell lines.ResultsWe have observed that WNVKUN in fact replicates with a greater rate and to higher titres that ZIKV in these cell lines.ConclusionsThese results would indicate the potential for all flaviviruses to replicate in placental tissue but it is the ability to cross the placenta itself that is the restrictive factor in the clinical progression and presentation of congenital Zika syndrome.

Tracing the Origin, Spread, and Molecular Evolution of Zika Virus in Puerto Rico, 2016-2017.

We reconstructed the 2016–2017 Zika virus epidemic in Puerto Rico by using complete genomes to uncover the epidemic’s origin, spread, and evolutionary dynamics. Our study revealed that the epidemic was propelled by multiple introductions that spread across the island, intricate evolutionary patterns, and ≈10 months of cryptic transmission.

Hide and Seek: The Interplay Between Zika Virus and the Host Immune Response.

Zika virus (ZIKV) received worldwide attention over the past decade when outbreaks of the disease were found to be associated with severe neurological syndromes and congenital abnormalities. Unlike most other flaviviruses, ZIKV can spread through sexual and transplacental transmission, adding to the complexity of Zika pathogenesis and clinical outcomes. In addition, the spread of ZIKV in flavivirus-endemic regions, and the high degree of structural and sequence homology between Zika and its close cousin Dengue have raised questions on the interplay between ZIKV and the pre-existing immunity to other flaviviruses and the potential immunopathogenesis. The Zika epidemic peaked in 2016 and has affected over 80 countries worldwide. The re-emergence of large-scale outbreaks in the future is certainly a possibility. To date, there has been no approved antiviral or vaccine against the ZIKV. Therefore, continuing Zika research and developing an effective antiviral and vaccine is essential to prepare the world for a future Zika epidemic. For this purpose, an in-depth understanding of ZIKV interaction with many different pathways in the human host and how it exploits the host immune response is required. For successful infection, the virus has developed elaborate mechanisms to escape the host response, including blocking host interferon response and shutdown of certain host cell translation. This review provides a summary on the key host factors that facilitate ZIKV entry and replication and the mechanisms by which ZIKV antagonizes antiviral innate immune response and involvement of adaptive immune response leading to immunopathology. We also discuss how ZIKV modulates the host immune response during sexual transmission and pregnancy to induce infection, how the cross-reactive immunity from other flaviviruses impacts ZIKV infection, and provide an update on the current status of ZIKV vaccine development.

Leu-to-Phe substitution at prM146 decreases the growth ability of Zika virus and partially reduces its pathogenicity in mice

Zika virus (ZIKV) is a mosquito-borne flavivirus that causes febrile illness. The recent spread of ZIKV from Asia to the Americas via the Pacific region has revealed unprecedented features of ZIKV, including transplacental congenital infection causing microcephaly. Amino acid changes have been hypothesized to underlie the spread and novel features of American ZIKV strains; however, the relationship between genetic changes and the epidemic remains controversial. A comparison of the characteristics of a Southeast Asian strain (NIID123) and an American strain (PRVABC59) revealed that the latter had a higher replication ability in cultured cells and higher virulence in mice. In this study, we aimed to identify the genetic region of ZIKV responsible for these different characteristics using reverse genetics. A chimeric NIID123 strain in which the E protein was replaced with that of PRVABC59 showed a lower growth ability than the recombinant wild-type strain. Adaptation of the chimeric NIID123 to Vero cells induced a Phe-to-Leu amino acid substitution at position 146 of the prM protein; PRVABC59 also has Leu at this position. Leu at this position was found to be responsible for the viral replication ability and partially, for the pathogenicity in mouse testes.

Blockade of Autocrine CCL5 Responses Inhibits Zika Virus Persistence and Spread in Human Brain Microvascular Endothelial Cells.

ABSTRACTZika virus (ZIKV) is a neurovirulent flavivirus that uniquely causes fetal microcephaly, is sexually transmitted, and persists in patients for up to 6 months. ZIKV persistently infects human brain microvascular endothelial cells (hBMECs) that form the blood-brain barrier (BBB) and enables viral spread to neuronal compartments. We found that CCL5, a chemokine with prosurvival effects on immune cells, was highly secreted by ZIKV-infected hBMECs. Although roles for CCL5 in endothelial cell (EC) survival remain unknown, the presence of the CCL5 receptors CCR3 and CCR5 on ECs suggested that CCL5 could promote ZIKV persistence in hBMECs. We found that exogenous CCL5 induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in hBMECs and that ERK1/2 cell survival signaling was similarly activated by ZIKV infection. Neutralizing antibodies to CCL5, CCR3, or CCR5 inhibited persistent ZIKV infection of hBMECs. While knockout (KO) of CCL5 failed to prevent ZIKV infection of hBMECs, at 3 days postinfection (dpi), we observed a >90% reduction in ZIKV-infected CCL5-KO hBMECs and a multilog reduction in ZIKV titers. In contrast, the addition of CCL5 to CCL5-KO hBMECs dose-dependently rescued ZIKV persistence in hBMECs. Inhibiting CCL5 responses using CCR3 (UCB35625) and CCR5 (maraviroc) receptor antagonists reduced the number of ZIKV-infected hBMECs and ZIKV titers (50% inhibitory concentrations [IC50s] of 2.5 to 12 μM), without cytotoxicity (50% cytotoxic concentration [CC50] of >80 μM). These findings demonstrate that ZIKV-induced CCL5 directs autocrine CCR3/CCR5 activation of ERK1/2 survival responses that are required for ZIKV to persistently infect hBMECs. Our results establish roles for CCL5 in ZIKV persistence and suggest the potential for CCL5 receptor antagonists to therapeutically inhibit ZIKV spread and neurovirulence.