Zika Virus Transmission Research Articles

Inactivation of Zika virus in plasma and derivatives by four different methods.

Zika virus (ZIKV) is an emerging arbovirus with increasing prevalence in recent years. To reduce the risk of ZIKV transmission by transfusion, some mitigation strategies were recommended based on pathogen reduction technologies for blood products. In this study, we aimed to study the efficacy of several common pathogen reduction methods in the inactivation of ZIKV. The fresh frozen plasma and derivatives were spiked with a high titer of ZIKV or Sindbis virus (SINV). Viral titers and ZIKV RNA were measured before and after the inactivation treatment by methylene blue (MB), solvent/detergent (S/D), pasteurization, and low pH. The mean ZIKV infectivity titers in plasma and derivatives were 7.08 ± 0.14, 5.17 ± 0.14, 7.08 ± 0.14, and 5.80 ± 0.14 log10 TCID50 /mL, respectively before MB, S/D, pasteurization, and low pH inactivation. We found no detectable ZIKV RNA after five successive passages of inoculation on host cells, indicating there is no infectivity after inactivation. Similar inactivation results were observed for SINV. In conclusion, we achieved robust ZIKV inactivation through the four inactivation procedures in several blood products. These findings suggest that the pathogen reduction technologies commonly applied in plasma and derivatives have the capacity to mitigate the risk of ZIKV transmission by transfusion.

First report on the transmission of Zika virus by Aedes (Stegomyia) aegypti (L.) (Diptera: Culicidae) during the 2018 Zika outbreak in India

In a recent outbreak of Zika virus (ZIKV) infection in Jaipur city (Rajasthan, India), a total of 159 cases were reported in September 2018. In order to identify vector responsible for Zika transmission, mosquitoes were collected from houses with reported Zika cases and nearby houses. A total of 108 pools containing 522 mosquitoes were tested for presence of ZIKV using RT-PCR and Real Time RT-PCR. We detected presence of ZIKV in three pools of Aedes (Stegomyia) aegypti (L.), out of a total of 79 pools with 383 Ae. aegypti through RT-PCR as well as real-time RT-PCR. The presence of ZIKV in Ae. aegypti was further confirmed by DNA sequencing of the partial envelope region of ZIKV. Homology search of DNA sequence revealed highest identity (100%) with a ZIKV isolate from human from the study area which support the role of Ae. aegypti acting as a ZIKV vector. All other mosquitoes (Aedes vittatus and Culex quinquefasciatus) were negative for ZIKV. None of the F1 generation mosquito pools (276 mosquitoes in 43 pools) were found positive. This is the first report of presence of ZIKV in Ae. aegypti from the Indian subcontinent.

Directional entry and release of Zika virus from polarized epithelial cells

BackgroundBoth vector borne and sexual transmission of Zika virus (ZIKV) involve infection of epithelial cells in the initial stages of infection. Epithelial cells are unique in their ability to form polarized monolayers and their barrier function. Cell polarity induces an asymmetry in the epithelial monolayer, which is maintained by tight junctions and specialized sorting machinery. This differential localization can have a potential impact of virus infection. Asymmetrical distribution of a viral receptor can restrict virus entry to a particular membrane while polarized sorting can lead to a directional release of virions. The present study examined the impact of cell polarity on ZIKV infection and release.MethodsA polarized Caco-2 cell model we described previously was used to assess ZIKV infection. Transepithelial resistance (TEER) was used to assess epithelial cell polarity, and virus infection was measured by immunofluorescence microscopy and qRT-PCR. Cell permeability was measured using a fluorescein leakage assay. Statistical significance was calculated using one-way ANOVA and significance was set at p < 0.05.ResultsUsing the Caco-2 cell model for polarized epithelial cells, we report that Zika virus preferentially infects polarized cells from the apical route and is released vectorially through the basolateral route. Our data also indicates that release occurs without disruption of cell permeability.ConclusionsOur results show that ZIKV has directional infection and egress in a polarized cell system. This mechanism of directional infection may be one of the mechanisms that enables the cross the epithelial barrier effectively without a disruption in cell monolayer integrity. Elucidation of entry and release characteristics of Zika virus in polarized epithelial cells can lead to better understanding of virus dissemination in the host, and can help in developing effective therapeutic interventions.

Views and Experiences of Travelers from US States to Zika-Affected Areas.

Travelers to areas with Zika virus transmission are at risk of infection and of transmitting the virus after returning home. While protective behaviors during and after travel can reduce these risks, information about traveler practices or underlying views is limited. We examined these issues using data from the first representative poll of travelers from US states to Zika-affected areas, including US territories and Miami, Florida, conducted December 1 to 23, 2016. We analyzed results among all travelers (n = 1,285) and 2 subgroups at risk for pregnancy-related complications: (1) travelers in households where someone was pregnant or considering pregnancy (n = 72), and (2) other travelers of reproductive age (n = 631). We also examined results among those with different levels of awareness and knowledge about Zika virus. Results show that in households where someone was pregnant or considering pregnancy, awareness of Zika in the destination, concern about infection, and adoption of protective behaviors was relatively high. That said, sizable shares of travelers as a whole did not know information about asymptomatic and sexual transmission or post-travel behaviors. Further, concern about getting infected during travel was low among travelers as a whole, including other travelers of reproductive age. Few travelers consistently adopted protective behaviors during or after travel. Even among travelers who were aware of Zika in their destination and knew how to protect themselves, adoption of protective behaviors was only slightly higher. Findings from this poll suggest communications may be more effective if tailored to different levels of true and perceived risk. To address gaps in knowledge about transmission and post-travel protective behaviors, messaging should include facts and acknowledge the complexities of novel information and social context. Consideration should also be given to emphasizing other benefits of Zika protective behaviors or prioritizing behaviors that are most feasible.

Natural Vertical Transmission of Zika Virus in Larval Aedes aegypti Populations, Morelos, Mexico.

We characterized natural vertical transmission of Zika virus in pools of Aedes aegypti larvae hatched from eggs collected in Jojutla, Morelos, Mexico. Of the 151 pools analyzed, 17 tested positive for Zika virus RNA; infectious Zika virus was successfully isolated from 1 of the larvae pools (31N) in C6/36 cells. Real-time quantitative PCR and indirect immunofluorescence assays confirmed the identity of the isolate, named Zika virus isolate 31N; plaque assays in Vero cells demonstrated the isolate’s infectivity in a mammalian cell line. We obtained the complete genome of Zika virus isolate 31N by next-generation sequencing and identified 3 single-nucleotide variants specific to Zika virus isolate 31N using the meta-CATS tool. These results demonstrate the occurrence of natural vertical transmission of Zika virus in wild Ae. aegypti mosquitoes and suggest that this transmission mode could aid in the spread and maintenance of Zika virus in nature.

Vertical transmission of Zika virus and perinatal microcephaly

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) transmitted primarily by Aedes mosquitoes. ZIKV can be transmitted to humans by non-vector borne mechanisms such as sexual intercourse, maternal-foetal transmission or blood transfusion. In 2015, ZIKV emerged in the Americas, and spread to 87 countries and territories with autochthonous transmission, distributed across four of the six WHO regions. Most ZIKV infections in pregnancy are asymptomatic, but mother to child transmission of the virus can occur in 20 to 30% of cases and cause severe foetal and child defects. Children exposed to ZIKV while in utero might develop a pattern of structural anomalies and functional disabilities secondary to central nervous system damage, known as congenital Zika syndrome, and whose most common clinical feature is microcephaly. Normocephalic children born to mothers with ZIKV infection in pregnancy, and with no observable Zika-associated birth defects, may also present with later neurodevelopmental delay or post-natal microcephaly. Screening and detection of ZIKV infection in pregnancy is essential, because most women with ZIKV infection are asymptomatic and clinical manifestations are non-specific. However, the diagnosis of ZIKV infection poses multiple challenges due to limited resources and scarce laboratory capabilities in most affected areas, the narrow window of time that the virus persists in the bloodstream, the large proportion of asymptomatic infections, and the cross-reactivity with other flaviviruses such as Dengue virus (DENV). Molecular methods (RT-PCR) are the most reliable tool to confirm ZIKV infection, as serodiagnosis requires confirmation with neutralization tests in case of inconclusive or positive serology results. Prenatal ultrasound assessment is essential for monitoring foetal development and early detection of possible severe anomalies. A mid- and long-term follow-up of children exposed to ZIKV while in utero is necessary to promptly detect clinical manifestations of possible neurological impairment.Tweetable abstract: Zika virus infection during pregnancy is a cause of pregnancy loss and disability in children. Protection against mosquito bites, access to sexual and reproductive health services, prompt screening and detection of ZIKV infection in pregnancy, and prenatal ultrasound monitoring are key control strategies whilst a vaccine is not available.

A32 Genomic surveillance of Zika virus transmission in the Amazonas State, Brazil

Zika virus (ZIKV) has caused an unprecedented epidemic linked to severe congenital syndromes. Transmission of ZIKV in the Americas was first confirmed in May 2015 in northeast Brazil, though the virus was likely introduced 1–2 years prior to its detection. Manaus, the capital city of the Amazonas State, the largest territory of any state in Brazil and the main economic center in the northern region, reported between 2016 and 2017 more than 2,327 suspected cases of ZIKV infection. To gain insights into the timing, source, and likely route(s) of ZIKV introduction in the Amazonas State, we tracked the virus by sequencing ZIKV genomes from infected patients. Using nanopore sequencing technology, we generated 56 Brazilian ZIKV genomes from Manaus city in the Amazonas state, sampled from human cases. On the basis of available sequences of isolates from the Americas, the Manaus sequences, we analyzed fell within a single strongly supported monophyletic clade (bootstrap support = 99%, posterior support = 1.00) that belongs to the Asian genotype. Genetic analysis suggests the outbreak most likely originated from transmission cycles not previously identified in North Brazil and not from a separate introduction into the Americas. Molecular dating analysis indicates that the outbreak was caused by a single founder strain that is estimated to have arrived in Manaus around February 2015. By analyzing surveillance and genetic data, we discovered that ZIKV moved among transmission zones in Manaus. Geographical analysis further indicates that the Northern part of the Manaus regions has a high transmission potential for ZIKV. Our work illustrates that near-real time genomics in the field can augment traditional approaches to infectious disease surveillance and control. Estimated dates for the international spread of ZIKV from the north region indicate the persistence of the virus transmission in recipient regions. Our study provides an understanding of how ZIKV initiates transmission in new regions.

Travel Surveillance and Genomics Uncover a Hidden Zika Outbreak during the Waning Epidemic.

SummaryThe Zika epidemic in the Americas has challenged surveillance and control. As the epidemic appears to be waning, it is unclear whether transmission is still ongoing, which is exacerbated by discrepancies in reporting. To uncover locations with lingering outbreaks, we investigated travel-associated Zika cases to identify transmission not captured by reporting. We uncovered an unreported outbreak in Cuba during 2017, a year after peak transmission in neighboring islands. By sequencing Zika virus, we show that the establishment of the virus was delayed by a year and that the ensuing outbreak was sparked by long-lived lineages of Zika virus from other Caribbean islands. Our data suggest that, although mosquito control in Cuba may initially have been effective at mitigating Zika virus transmission, such measures need to be maintained to be effective. Our study highlights how Zika virus may still be “silently” spreading and provides a framework for understanding outbreak dynamics.Video

Experimental Assessment of Zika Virus Mechanical Transmission by Aedes Aegypti.

The pandemic emergence of several mosquito-borne viruses highlights the need to understand the different ways in which they can be transmitted by vectors to human hosts. In this study, we evaluated the propensity of Aedes aegypti to transmit mechanically Zika virus (ZIKV) using an experimental design. Mosquitoes were allowed to feed on ZIKV-infected blood and were then rapidly transferred to feed on ZIKV-free blood until they finished their meal. The uninfected blood meals, the mosquito abdomens, as well as the mouthparts dissected from fully and partially engorged mosquitoes were analyzed using RT-qPCR and/or virus titration. All the fully engorged mosquito abdomens were ZIKV-infected, whereas their mouthparts were all ZIKV-negative. Nonetheless, one of the partially engorged mosquitoes carried infectious particles on mouthparts. No infectious virus was found in the receiver blood meals, while viral RNA was detected in 9% of the samples (2/22). Thus, mechanical transmission of ZIKV may sporadically occur via Ae. aegypti bite. However, as the number of virions detected on mouthparts (2 particles) is not sufficient to induce infection in a naïve host, our results indicate that mechanical transmission does not impact ZIKV epidemiology.

Physicians' knowledge, attitudes and practices towards Zika virus infection in Jordan.

Zika virus (ZIKAV) disease is a public health problem of international concern. Recent evidence has documented imported ZIKAV cases into the Middle East and the existence of ZIKAV-transmitting mosquitoes in Jordan. However, limited data exist on the role of physicians in public awareness in this regard. This study aimed to assess ZIKAV knowledge, attitudes and counseling practices (KAP) of general physicians and gynecologists in Amman, Jordan. In this cross-sectional study, a structured paper-based questionnaire was completed by 119 participants during 2016-2017. Only 4.2% of the physicians correctly addressed ZIKAV-complication questions. A misconception of considering direct contact between individuals and breastfeeding as modes of ZIKAV transmission was observed. Only one participant correctly recognized that isolation of infected or exposed persons is not recommended. Having at least five years of experience in medical practice was the only factor that was significantly associated with a high knowledge score (P-value=0.011). Although prevention measures are the sole method to control ZIKAV spread, only 50% of participants believed in the efficacy of such measures. Despite a quarter of participants perceiving ZIKAV as a threat to their patients, none of them have counseled a patient in this regard before. The presence of an evidence of ZIKAV in Jordan and health authorities' recommendations were the most important predictors for adoption of counseling practice. General physicians and gynecologists in Jordan had several gaps in knowledge of key aspects of ZIKAV disease, and there is a need for specific training programs of physicians and gynecologists.

A CRISPR Activation Screen Identifies Genes That Protect against Zika Virus Infection.

Zika virus (ZIKV) is an arthropod-borne emerging pathogen causing febrile illness. ZIKV is associated Guillain-Barré syndrome and other neurological complications. Infection during pregnancy is associated with pregnancy complications and developmental and neurological abnormalities collectively defined as congenital Zika syndrome. There is still no vaccine or specific treatment for ZIKV infection. To identify host factors that can rescue cells from ZIKV infection, we used a genome-scale CRISPR activation screen. Our highly ranking hits included a short list of interferon-stimulated genes (ISGs) previously reported to have antiviral activity. Validation of the screen results highlighted interferon lambda 2 (IFN-λ2) and interferon alpha-inducible protein 6 (IFI6) as genes providing high levels of protection from ZIKV. Activation of these genes had an effect on an early stage in viral infection. In addition, infected cells expressing single guide RNAs (sgRNAs) for both of these genes displayed lower levels of cell death than did the controls. Furthermore, the identified genes were significantly induced in ZIKV-infected placenta explants. Thus, these results highlight a set of ISGs directly relevant for rescuing cells from ZIKV infection or its associated cell death and substantiate CRISPR activation screens as a tool to identify host factors impeding pathogen infection.IMPORTANCE Zika virus (ZIKV) is an emerging vector-borne pathogen causing a febrile disease. ZIKV infection might also trigger Guillain-Barré syndrome, neuropathy, and myelitis. Vertical transmission of ZIKV can cause fetus demise, stillbirth, or severe congenital abnormalities and neurological complications. There is no vaccine or specific antiviral treatment against ZIKV. We used a genome-wide CRISPR activation screen, where genes are activated from their native promoters to identify host cell factors that protect cells from ZIKV infection or associated cell death. The results provide a better understanding of key host factors that protect cells from ZIKV infection and might assist in identifying novel antiviral targets.

European Aedes caspius mosquitoes are experimentally unable to transmit Zika virus

BackgroundAedes caspius (Pallas, 1771) is a floodwater mosquito species widely distributed in the Western Palaearctic. As an anthropophilic species, its role as an arbovirus vector may be the key for understanding the transmission cycle of certain diseases in Europe such as Zika virus (ZIKV). Concerning vector competence for ZIKV, studies related to Ae. caspius are still scarce. ZIKV is an arbovirus that has provoked a widespread epidemic in the Pacific region (2007–2013) and in the Americas (2015–2016). ZIKV is associated with serious neurological injuries (e.g. microcephaly) and Guillain-Barré syndrome. Due to the ZIKV epidemics in the American continent, some viraemic travellers coming from endemic countries have been reported in Europe. More knowledge is therefore required to define the susceptibility of autochthonous mosquito species such as Ae. caspius for ZIKV in order to improve arbovirus surveillance and control programmes. In the present study, the vector competence of a European population of Ae. caspius was evaluated for two ZIKV lineages, the Suriname ZIKV strain (Asian lineage) and the MR766 ZIKV strain (African I lineage). Females were tested at 7, 14 and 21 days post-exposure (dpe) to infectious blood meals. An Ae. aegypti PAEA strain was used as a positive control.ResultsAedes caspius presented low susceptibility to ZIKV infection and the virus was only detected by RT-qPCR in body samples. Low viral loads were detected for the MR766 strain at 7 dpe and for the Suriname strain at 14 and 21 dpe. Aedes caspius was unable to produce a disseminated infection and virus transmission at any of the tested time points. Using Ae. aegypti PAEA strain, infection, dissemination and transmission rates were calculated for the Suriname ZIKV strain (Asian lineage) at each time point. For the MR766 ZIKV strain (African I lineage), while only infection rates were estimated at each time point, no dissemination or transmission were detected in either species.ConclusionsThe results of the present study reveal that the tested Ae. caspius population has a strong midgut escape barrier that limits the dissemination or transmission of the virus. As such, it seems unlikely that European Ae. caspius mosquitoes could be involved in ZIKV transmission if ZIKV was introduced into Europe. This information may help in designing a better strategy to European surveillance and control programmes for ZIKV.

Risk assessment and genomic characterization of Zika virus in China and its surrounding areas.

Zika virus (ZIKV) has emerged as a global pathogen causing significant public health concerns. China has reported several imported cases where ZIKV were carried by travelers who frequently travel between China and ZIKV-endemic regions. To fully characterize the ZIKV strains isolated from the cases reported in China and assess the risk of ZIKV transmission in China, comprehensive phylogenetic and genetic analyses were performed both on all ZIKV sequences of China and on a group of scientifically selected ZIKV sequences reported in some of the top interested destinations for Chinese travelers. ZIKV genomic sequences were retrieved from the National Center for Biotechnology Information database through stratified sampling. Recombination event detection, maximum likelihood (ML) phylogenetic analysis, molecular clock analysis, selection pressure analysis, and amino acid substitution analysis were used to reconstruct the epidemiology and molecular transmission of ZIKV. The present study investigated 18 ZIKV sequences from China and 70 sequences from 16 selected countries. Recombination events rarely happens in all ZIKV Asian lineage. ZIKV genomes were generally undergone episodic positive selection (17 sites), and only one site was under pervasive positive selection. All ZIKV imported into China were Asian lineage and were assigned into two clusters: Venezuela-origin (cluster A) and Samoa-origin cluster (cluster B) with common ancestor from French Polynesia. The time of most recent common ancestors of Cluster A dated to approximately 2013/11 (95% highest posterior density [HPD] 2013/06, 2014/03) and cluster B dated to 2014/08 (95% HPD 2014/02, 2015/01). Cluster B is more variable than Cluster A in comparison with other clusters, but no varied site of biological significance was revealed. ZIKV strains in Southeast Asia countries are independent from strains in America epidemics. The genetic evolution of ZIKV is conservative. There are two independent introductions of ZIKV into China and China is in danger of autochthonous transmission of ZIKV because of high-risk surrounding areas. Southeast Asia areas have high risk of originating the next large-scale epidemic ZIKV strains.

The Dual Role of the Immune Response in Reproductive Organs During Zika Virus Infection

Zika virus is a mosquito-borne viral disease that emerged as a significant health problem in the Americas after an epidemic in 2015. Especially concerning are cases where Zika is linked to the development of brain abnormalities in newborns. Unlike other flaviviruses, Zika can be transmitted sexually, increasing the potential for intraspecies infection. Several reports show that the virus can persist for months in the testis of males after clearance of viremia, and that females are highly susceptible to infection via sexual transmission. The most common route of sexual transmission is male-to-female, which suggests that the mechanism driving persistence of Zika in the testis is essential for dissemination. The immune system plays an essential role in Zika infection. In females, a robust response inhibits the virus to control the infection. In males, however, the immunological response to Zika infection correlates with viral persistence. Thus, the immune system may have a dual role in sexually transmitted pathogenesis. The mechanism by which the immune system allows the virus to enter an immune-privileged site while continuing to disseminate is unclear. In this mini-review, we highlight advances in our knowledge of sexually transmitted Zika virus pathogenesis and the possible mechanisms mounted by the immune system that control or exacerbate the infection.

Zika Virus Transmission Through Blood Tissue Barriers.

The recent Zika virus (ZIKV) epidemic in the Americas and the Caribbean revealed a new deadly strain of the mosquito-borne virus, which has never been associated with previous outbreaks in Asia. For the first time, widespread ZIKV infection was shown to cause microcephaly and death of newborns, which was most likely due to the mutation acquired during the large outbreak recorded in French Polynesia in 2013–2014. Productive ZIKV replication and persistence has been demonstrated in placenta and fetal brains. Possible association between ZIKV and microcephaly and fetal death has been confirmed using immunocompetent mouse models in vitro and in vivo. Having crossed the placenta, ZIKV directly targets neural progenitor cells (NPCs) in developing human fetus and triggers apoptosis. The embryonic endothelial cells are exceptionally susceptible to ZIKV infection, which causes cell death and tissue necrosis. On the contrary, ZIKV infection does not affect the adult brain microvascular cell morphology and blood–brain barrier function. ZIKV is transmitted primarily by Aedes mosquito bite and is introduced into the placenta/blood through replication at the site of the entry. Also, virus can be transmitted through unprotected sex. Although, multiple possible routes of virus infection have been identified, the exact mechanism(s) utilized by ZIKV to cross the placenta still remain largely unknown. In this review, the current understanding of ZIKV infection and transmission through the placental and brain barriers is summarized.

Protective Efficacy of Nucleic Acid Vaccines Against Transmission of Zika Virus During Pregnancy in Mice.

Zika virus (ZIKV) caused an epidemic of congenital malformations in 2015-2016. Although many vaccine candidates have been generated, few have demonstrated efficacy against congenital ZIKV infection. Here, we evaluated lipid-encapsulated messenger RNA (mRNA) vaccines and a DNA plasmid vaccine encoding the prM-E genes of ZIKV in mouse models of congenital infection. Although the DNA vaccine provided comparable efficacy against vertical transmission of ZIKV, the mRNA vaccines, including one that minimizes antibody-dependent enhancement of infection, elicited higher levels of antigen-specific long-lived plasma cells and memory B cells. Despite the induction of robust neutralizing antibody titers by all vaccines, breakthrough seeding of the placenta and fetal head was observed in a small subset of type I interferon signaling-deficient immunocompromised dams. In comparison, evaluation of one of the mRNA vaccines in a human STAT2-knockin transgenic immunocompetent mouse showed complete protection against congenital ZIKV transmission. These data will inform ongoing human ZIKV vaccine development efforts and enhance our understanding of the correlates of vaccine-induced protection.

Female-to-male sexual transmssion of Zika virus infection

Dear Editor, We read the publication on ‘The challenge given by Zika virus’ with a great interest.[1][1] Rodriguez and Sebastian mentioned that ‘ No sexual transmission of Zika virus from...

First report case with negative genetic study (array CGH, exome sequencing) in patients with vertical transmission of Zika virus infection and associated brain abnormalities.

IntroductionZika virus (ZIKV) is a little-known emerging mosquito-borne flavivirus. The perinatal ZIKV infection was associated with birth defects during the Brazilian outbreak. There was an increased risk of intrauterine transmission of the virus and a marked increase in the number of newborns with microcephaly. We report on two such cases.Case ReportThe first case was a 25-year-old pregnant woman from Colombia who became acutely ill with general symptoms during the tenth week of gestation, followed by severe generalized itching and maculopapular rash for approximately five days. This case was reported during the epidemic stage of the ZIKV infection in Colombia. At 23.3 gestational weeks, ultrasonography showed abnormal intracranial anatomy with cerebral ventriculomegaly, microcephaly, and parenchymal calcification. Given the grave prognosis, the patient elected to terminate the pregnancy at 25 gestational weeks. The second case was a 24-year-old pregnant woman who became acutely ill during the 17th week of gestation, which corresponded with the ZIKV epidemic in Colombia. At 30.5 gestational weeks, ultrasonography showed isolated fetal cerebral ventriculomegaly. We detected ZIKV in the amniotic fluid; however, the virus was not detected in the urine or serum of the mother or fetus. Tests for dengue virus, chikungunya virus, Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus, HIV, hepatitis B and C, and parvovirus B19 were all negative. Different samples obtained from the placenta, amniotic liquid, and cerebrospinal fluid were positive for viral isolation of ZIKV RNA using TaqMan RT-PCR. Additionally, the parents and fetuses were tested for genetic diseases using whole exome sequencing and array CGH to rule out possible genetic syndromes that produce these congenital abnormalities.ConclusionThese were the first cases in Colombia to show early vertical transmission of ZIKV and the first cases associated with congenital cerebral abnormalities in which molecular, infectious, and genomic tests were performed.

Chloroquine inhibits endosomal viral RNA release and autophagy-dependent viral replication and effectively prevents maternal to fetal transmission of Zika virus

Zika virus (ZIKV) infection can cause neonatal microcephaly and neurological disorders. Currently, there is no designated drug for treating ZIKV infection and preventing neonatal microcephaly. In this study, we evaluated the effect of chloroquine, an anti-malaria drug, in ZIKV infected cells and mouse models. Chloroquine significantly inhibited ZIKV infection in multiple mammalian cell lines. Chloroquine treatment significantly improved the survival of ZIKV-infected 1-day old suckling SCID Beige mice and reduced viremia in adult SCID Beige mice. Importantly, chloroquine protected the fetus from maternal infection by reducing placenta to fetus viral transmission. We found that chloroquine exerts at least two mechanisms in protecting against ZIKV infection: 1) inhibiting endosomal disassembly of the internalized virus and thus reducing the release of viral RNA to the cytoplasm for replication; 2) inhibiting ZIKV RNA replication through blocking ZIKV induced autophagy. Our study suggests that chloroquine treatment warrants to be considered as a mitigation strategy for treating ZIKV infection and preventing ZIKV-associated microcephaly in pregnant women.

The Zika Virus Epidemic Four Years After: Where are We?

Zika virus (ZIKV), an emerging arthropod-borne, single-stranded RNA virus, member of the Spondweni serocomplex (genus Flavivirus, family Flaviviridae), was first isolated in 1947 from a sentinel (monkeys held captive with the purpose of identifying yellow fever activity) rhesus monkey in a forest in Uganda. After its discovery, ZIKV was associated only with few sporadic mild cases in humans in Africa and Asia over the next 60 years.[1] However, since 2007, when the first outbreak of ZIKV outside Africa and Asia was reported in the Federated States of Micronesia (Yap), it has been identified in subsequent outbreaks in French Polynesia, Pacific islands, and more recently, from 2015, Brazil was the first country in the Western Hemisphere to confirm autochthonous transmission of ZIKV associated with an outbreak of “dengue-like syndrome” cases.[2]