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1.
Cell Rep ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31956073

RESUMO

We perform a CRISPR-Cas9 genome-wide screen in glioblastoma stem cells and identify integrin αvß5 as an internalization factor for Zika virus (ZIKV). Expression of αvß5 is correlated with ZIKV susceptibility in various cells and tropism in developing human cerebral cortex. A blocking antibody against integrin αvß5, but not αvß3, efficiently inhibits ZIKV infection. ZIKV binds to cells but fails to internalize when treated with integrin αvß5-blocking antibody. αvß5 directly binds to ZIKV virions and activates focal adhesion kinase, which is required for ZIKV infection. Finally, αvß5 blocking antibody or two inhibitors, SB273005 and cilengitide, reduces ZIKV infection and alleviates ZIKV-induced pathology in human neural stem cells and in mouse brain. Altogether, our findings identify integrin αvß5 as an internalization factor for ZIKV, providing a promising therapeutic target, as well as two drug candidates for prophylactic use or treatments for ZIKV infections.

2.
Bioorg Med Chem Lett ; 30(4): 126906, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31902708

RESUMO

The prevalence of Zika virus (ZIKV) has become widespread in recent years. ZIKV infection is associated with severe congenital CNS malformations in both newborns and adults. However, neither vaccines nor therapeutics are available to control ZIKV infection until now. We started by hit screening our in-house small molecule library, then designed, synthesized, and evaluated a new class of 1, 4-bibenzylsubstituted piperazine derivatives for their cytopathic effect (CPE) protection effect in a ZIKV-infected Vero E6 cellular assay. A preliminary structure-activity relationship study identified five novel 4-amino-2-(4-benzylpiperazin-1-yl)methylbenzonitrile analogs with obvious CPE reduction effects against ZIKV at micromolar concentrations. Moreover, compound 3p exerted a significant antiviral effect on both Zika RNA replication and virus protein expression in a dose-dependent manner at low micromolar concentrations. This study demonstrated the potential of a novel 4-amino-2-(4-benzylpiperazin-1-yl)methylbenzonitrile scaffold for the development of anti-ZIKV candidates.

3.
Viruses ; 12(1)2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31947825

RESUMO

Zika virus (ZIKV) emerged in the Americas in 2015, presenting unique challenges to public health. Unlike other arboviruses of the Flaviviridae family, it is transmissible by sexual contact, which facilitates the spread of the virus into new geographic areas. Additionally, ZIKV can be transmitted from mother to fetus, causing microcephaly and other severe developmental abnormalities. Reliable and easy-to-work-with clones of ZIKV expressing heterologous genes will significantly facilitate studies aimed at understanding the virus pathogenesis and tissue tropism. Here, we developed and characterized two novel approaches for expression of heterologous genes of interest in the context of full-length ZIKV genome and compared them to two previously published strategies for ZIKV-mediated gene expression. We demonstrated that among the four tested viruses expressing nLuc gene, the virus constructed using a newly developed approach of partial capsid gene duplication (PCGD) attained the highest titer in Vero cells and resulted in the highest level of nLuc expression. Suitability of the PCGD approach for expression of different genes of interest was validated by replacing nLuc sequence with that of eGFP gene. The generated constructs were further characterized in cell culture. Potential applications of ZIKV clones stably expressing heterologous genes include development of detection assays, antivirals, therapeutics, live imaging systems, and vaccines.

4.
Cells ; 9(1)2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31947958

RESUMO

To date, no safe vaccine or antivirals for Zika virus (ZIKV) infection have been found. The pathogenesis of severe Zika, where host and viral factors participate, remains unclear. For the control of Zika, it is important to understand how ZIKV interacts with different host cells. Knowledge of the targeted cellular pathways which allow ZIKV to productively replicate and/or establish prolonged viral persistence contributes to novel vaccines and therapies. Monocytes and endothelial vascular cells are the main ZIKV targets. During the infection process, cells are capable of releasing extracellular vesicles (EVs). EVs are mediators of intercellular communication. We found that mosquito EVs released from ZIKV-infected (C6/36) cells carry viral RNA and ZIKV-E protein and are able to infect and activate naïve mosquito and mammalian cells. ZIKV C6/36 EVs promote the differentiation of naïve monocytes and induce a pro-inflammatory state with tumor necrosis factor-alpha (TNF-α) mRNA expression. ZIKV C6/36 EVs participate in endothelial vascular cell damage by inducing coagulation (TF) and inflammation (PAR-1) receptors at the endothelial surface of the cell membranes and promote a pro-inflammatory state with increased endothelial permeability. These data suggest that ZIKV C6/36 EVs may contribute to the pathogenesis of ZIKV infection in human hosts.

5.
PLoS Negl Trop Dis ; 14(1): e0007970, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31961867

RESUMO

BACKGROUND: Arboviruses transmitted by day-biting Aedes mosquitoes are a major public health concern. With the challenges inherent in arbovirus vaccine and therapeutics development, vector control and bite prevention strategies are among the limited options available for immediate intervention. Bite prevention through personal protective technologies (PPT), such as topical mosquito repellents or repellent-impregnated clothing, may help to decrease biting rates and, therefore, the risk of disease in groups most susceptible to adverse outcomes from Zika virus. However, achieving high uptake and compliance with PPT can be challenging. METHODOLOGY/PRINCIPAL FINDINGS: To gain an insight into the knowledge and concerns of pregnant women surrounding Zika and their opinions regarding PPT, particularly repellent clothing, a focus group study was carried out with pregnant women, women of reproductive age, and semi-structured interviews with their male partners in two cities in Colombia. The discussions revealed shortfalls in basic knowledge of Zika virus, with several pregnant participants reporting being unaware of the potential for Zika-related congenital malformations. Although participants generally considered Zika to be a significant personal threat, most rated it as less of a concern than dengue or diarrheal diseases. Overall, repellent clothing and other forms of PPT were viewed as effective, although some participants expressed concerns over the high costs of repellents, and safety fears of regular contact with repellent chemicals, which they perceived as potentially harmful. Plant-derived repellents were considered to be safer than synthetic chemical repellents. Discussions also highlighted that health centers were the preferred source of information on bite-reduction. CONCLUSIONS/SIGNIFICANCE: Achieving high uptake and compliance with PPT in populations most at risk of adverse outcomes from Zika infection requires engaging key users in open dialogue to identify and address any practical issues regarding PPT use, and concerns over safety. The findings presented here suggest that educational campaigns should strongly emphasize the risks associated with Zika during pregnancy, and discuss safety profiles of approved synthetic repellents and the availability of EPA-approved plant-based repellents. In addition, the economic and political context should be a major consideration when evaluating personal mosquito-repellent strategies.

6.
Infect Genet Evol ; : 104199, 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31962160

RESUMO

Zika virus (ZIKV) is an RNA virus that has spread through mosquito sting. Currently, no vaccine and antiviral medication available so far against ZIKV. Therefore, it has fostered a study to design MEBP vaccine enabling effective prevention against the ZIKV infection. In this study combination of immuno-informatics and molecular docking approach was used to constitute a MEBP vaccine. The ZIKV proteome was used for prediction of B-cell, T-cell (HTL & CTL) and IFN-γ epitopes. After prediction, highly antigenic and overlapping epitopes have been shortlisted which includes 14 CTL and 11 HTL epitopes that have been linked to the final peptide through AAY and GPGPG linkers respectively. An adjuvant at the N-end of the vaccine was added to improve the immunogenicity of the vaccine through the EAAAK linker. The final construct constitutes 435 amino acids after the addition of linkers and adjuvant. The existence of B-cell and IFN-γ epitopes affirms the humoral and cell-mediated immune responses acquired by the construct. Allergenicity, antigenicity and different physiochemical attributes of the vaccine were evaluated to assure its safety and immunogenicity profile. In fact, the construct was antigenic and non-allergenic. Docking was performed among vaccine and TLR-3 to evaluate the binding affinity and the molecular interaction. Finally, the construct was subjected to In silico cloning to confers the authenticity of its expression efficiency. However, the proposed construct need to be validate experimentally to ensure its safety and immunogenic profile.

7.
J Biomol Struct Dyn ; : 1-13, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31920173

RESUMO

Zika virus (ZIKV), belongs to the flavivirus genus and Flaviviridae family that associated with serious diseased conditions like microcephaly and other neurological disorders (Guillan-Barré syndrome). As there is no vaccine or therapies available against ZIKV to date. Hence, it is an unmet need to find potential drug candidates and target sites against Zika virus infection. NS2B-NS3 protease making an attractive target for therapeutic intervention in ZIKV infections because of its critical role in hydrolysis of a single polyprotein encoded by Zika virus. Recently, there are some experimental evidence about the flavonoids as Zika virus NS2B-NS3 protease inhibitors. However, molecular interaction between protease complex and inhibitors at atomic levels has not been explored. Here, we have taken the experimentally validated thirty-eight flavonoids inhibitors against NS2B-NS3 protease to examine the molecular interaction using molecular docking and molecular dynamics simulations. We found out few flavonoids such as EGCG and its two derivatives, isoquercetin, rutin and sanggenon O showing interaction with catalytic triad (His51, Asp75, and Ser135) of the active site of NS2B-NS3 protease and found to be stable throughout the simulation. Therefore it is evident that interaction with the catalytic triad playing a vital role in the inhibition of the enzyme activity as a result inhibition of the virus propagation. However these compounds can be explored further for understanding the mechanism of action of these compounds targeting NS2B-NS3 protease for inhibition of Zika virus.

8.
N C Med J ; 81(1): 14-22, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31908326

RESUMO

BACKGROUND The Zika virus (ZIKV) epidemic that began in 2015 presented a risk for ZIKV infection among persons who traveled to ZIKV-affected countries. Latinas in North Carolina and their sexual partners may be exposed to ZIKV when traveling to these regions.METHODS We administered a cross-sectional survey, measuring ZIKV risk and knowledge, to a convenience sample of 262 reproductive-age Latinas attending a Federally Qualified Health Center in rural North Carolina. We described ZIKV risk and knowledge in the sample, and compared responses between those who were pregnant or recently pregnant, and those who were not pregnant. We further identified factors associated with 1) awareness of ZIKV and 2) high knowledge of ZIKV sequelae and prevention among those who were aware of ZIKV, using log-binomial regression.RESULTS Two-thirds of participants had ever heard of ZIKV, which was positively associated with educational attainment. Most participants aware of ZIKV had moderate/high knowledge of ZIKV transmission (92.5%) and symptoms (73.2%), but knowledge of preventing sexual and congenital transmission was limited. Travel was infrequent among pregnant or recently pregnant participants (5.4%) and their partners (7.1%). Despite low risk for ZIKV infection, participants were willing to practice ZIKV prevention.LIMITATIONS Our study is limited by a lack of generalizability to Latinas in other regions of the country, self-reporting bias, and lack of survey validation as an indicator of English language proficiency.CONCLUSIONS Providers should identify patients likely to become pregnant and travel to high-risk areas, inquire about partner travel history, and offer culturally appropriate ZIKV risk counseling.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde/etnologia , Hispano-Americanos/psicologia , Doença Relacionada a Viagens , Infecção por Zika virus/etnologia , Estudos Transversais , Feminino , Hispano-Americanos/estatística & dados numéricos , Humanos , North Carolina , Gravidez , Fatores de Risco , Serviços de Saúde Rural
9.
Artigo em Inglês | MEDLINE | ID: mdl-31932383

RESUMO

Here, we report a class of tryptophan trimers and tetramers that inhibit (at low micromolar range) dengue and Zika virus infection in vitro These compounds (AL family) have three or four peripheral tryptophan moieties directly linked to a central scaffold through their amino groups, thus their carboxylic acid groups are free and exposed to the periphery. Structure activity relationship (SAR) studies demonstrated that the presence of extra phenyl rings with substituents other than COOH at the N1 or C2 positions of the indole side-chain is a requisite for the antiviral activity against both viruses. The molecules showed potent antiviral activity, with low cytotoxicity, when evaluated on different cell lines. Moreover, they were active against laboratory and clinical strains of all four serotypes of dengue virus as well as a selected group of Zika virus strains. Additional mechanistic studies performed with the two most potent compounds (AL439 and AL440) demonstrated an interaction with the viral envelope glycoprotein (domain III) of dengue 2 virus, thus preventing virus attachment to the host cell membrane. Since no antiviral agent is approved at the moment against these two flaviviruses, further pharmacokinetic studies with these molecules are needed for their development as future therapeutic/prophylactic drugs.

10.
Bull Math Biol ; 82(1): 13, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31933003

RESUMO

Although dengue and Zika cocirculation has increased within the past 5 years, very little is known about its epidemiological consequences. To investigate the effect of dengue and Zika cocirculation on the spread of both pathogens, we create a deterministic dengue and Zika coinfection model, the first to incorporate altered infectivity of mosquitoes (due to coinfection). The model also addresses increased infectivity due to antibody-dependent enhancement (ADE) within the human population. Central to our analysis is the derivation and interpretation of the basic reproductive number and invasion reproductive number of both pathogens. In addition, we investigate how model parameters impact the persistence of each disease. Our results identify threshold conditions under which one disease facilitates the spread of the other and show that ADE has a greater impact on disease persistence than altered vector infectivity. This work highlights the importance of ADE and illustrates that while the endemic presence of dengue facilitates the spread of Zika, it is possible for high Zika prevalence to prevent the establishment of dengue.

11.
Am J Trop Med Hyg ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31933455

RESUMO

During the 2016 Zika pandemic in Brazil, women's perceptions of infection risk, ability to adhere to Zika prevention strategies, or access to services following exposure were not emphasized in the public health response. Women in Fortaleza, Brazil, responded to a questionnaire on social factors related to perceived Zika risk and access to health care in June 2016. Data were coded using prespecified categories, and response frequency was reported. Of 37 respondents, most reported a lack of public services to support mosquito control (n = 19) or delayed access to reproductive health care (n = 14). Only 22% described specific maternal risks or fetal outcomes as a consequence of Zika infection. Respondents indicated an overall disconnect between public health efforts and women's perceptions of their reproductive control, including limited support concerning microcephaly in infants. Interventions targeting Zika may require a greater emphasis on strengthening health systems and infrastructure to realistically prevent transmission.

12.
Int J Mol Sci ; 21(2)2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31940993

RESUMO

Zika virus (ZIKV) is a new and emerging virus that has caused outbreaks worldwide. The virus has been linked to congenital neurological malformations in neonates and Guillain-Barré syndrome in adults. Currently there are no effective vaccines available. As a result, there is a great need for ZIKV treatment. In this study, we developed single chain variable fragment (scFv) antibodies that target the ZIKV envelope protein using phage display technology. We first induced an immune response in white leghorn laying hens against the ZIKV envelope (E) protein. Chickens were immunized and polyclonal immunoglobulin yolk (IgY) antibodies were extracted from egg yolks. A high-level titer of anti-ZIKV_E IgY antibodies was detected using enzyme-linked immunosorbent assay (ELISA) after the third immunization. The titer persisted for at least 9 weeks. We constructed two antibody libraries that contained 5.3 × 106 and 4.5 × 106 transformants. After biopanning, an ELISA phage assay confirmed the enrichment of specific clones. We randomly selected 26 clones that expressed ZIKV scFv antibodies and classified them into two groups, short-linker and long-linker. Of these, four showed specific binding activities toward ZIKV_E proteins. These data suggest that the polyclonal and monoclonal scFv antibodies have the diagnostic or therapeutic potential for ZIKV.

13.
JCI Insight ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910161

RESUMO

Dengue (DENV) and Zika viruses (ZIKV) are closely related mosquito-borne flaviviruses that co-circulate in tropical regions and constitute major threats to global human health. Whether preexisting immunity to one virus affects disease caused by the other during primary or secondary infections is unknown but is critical in preparing for future outbreaks and predicting vaccine safety. Using a human skin explant model, we show that DENV-3 immune sera increased recruitment and infection of Langerhans cells, macrophages and dermal dendritic cells following inoculation with DENV-2 or ZIKV. Similarly, ZIKV immune sera enhanced infection with DENV-2. Immune sera increased migration of infected Langerhans cells to dermis and emigration of infected cells out of skin. Heterotypic immune sera increased viral RNA in dermis almost tenfold and reduced the amount of virus required to infect a majority of myeloid cells by 100 to 1,000 fold. Enhancement was associated with cross-reactive IgG and induction of IL-10 expression and was mediated by both CD32 and CD64 Fcγ receptors. These findings reveal that preexisting heterotypic immunity greatly enhances DENV and ZIKV infection, replication and spread in human skin. This relevant tissue model will be valuable in assessing the efficacy and risk of dengue and Zika vaccines in humans.

14.
Sci Rep ; 10(1): 512, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949262

RESUMO

Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family that has been known to circulate for decades causing mild febrile illness. The more recent ZIKV outbreaks in the Americas and the Caribbean associated with congenital malformations and Guillain-Barré syndrome in adults have placed public health officials in high alert and highlight the significant impact of ZIKV on human health. New technologies to study the biology of ZIKV and to develop more effective prevention options are highly desired. In this study we demonstrate that direct delivery in mice of an infectious ZIKV cDNA clone allows the rescue of recombinant (r)ZIKV in vivo. A bacterial artificial chromosome containing the sequence of ZIKV strain Paraiba/2015 under the control of the cytomegalovirus promoter was complexed with a commercial transfection reagent and administrated using different routes in type-I interferon receptor deficient A129 mice. Clinical signs and death associated with ZIKV viremia were observed in mice. The rZIKV recovered from these mice remained fully virulent in a second passage in mice. Interestingly, infectious rZIKV was also recovered after intraperitoneal inoculation of the rZIKV cDNA in the absence of transfection reagent. Further expanding these studies, we demonstrate that a single intraperitoneal inoculation of a cDNA clone encoding an attenuated rZIKV was safe, highly immunogenic, and provided full protection against lethal ZIKV challenge. This novel in vivo reverse genetics method is a potentially suitable delivery platform for the study of wild-type and live-attenuated ZIKV devoid of confounding factors typical associated with in vitro systems. Moreover, our results open the possibility of employing similar in vivo reverse genetic approaches for the generation of other viruses and, therefore, change the way we will use reverse genetics in the future.

15.
Int J Gynaecol Obstet ; 148 Suppl 2: 45-54, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31975393

RESUMO

OBJECTIVES: To analyze the initial healthcare response to the Zika virus in Piura, Peru, and assess the perceptions of midwives and nurses regarding their role in prevention of Zika virus and management of congenital Zika syndrome (CZS). METHODS: This ethnographic study used a rapid qualitative assessment design. Data were collected through a focus group with midwives and in-depth interviews with midwives (n=11) and nurses (n=5). RESULTS: The focus of the early Zika virus response in Piura was on pregnant women and vector control. Midwives received some training on Zika-related care during the early response. Nurses did not receive any Zika-specific training. Neither nurses nor midwives were trained in neonatal CZS surveillance. Midwives were clear about the value and feasibility of incorporating Zika virus surveillance in their daily work, however nurses were not. They referred to lack of training and appropriate tools as limitations. Confusion about Zika virus and CZS symptomatology and effects persisted in both groups. Concerns about their own personal risk influenced the ways they engaged with Zika virus prevention in the community. CONCLUSION: Long-term management of endemic Zika virus in Piura will require the engagement of both nurses and midwives as primary care providers.

16.
Int J Gynaecol Obstet ; 148 Suppl 2: 15-19, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31975403

RESUMO

OBJECTIVES: To describe the mechanisms of implementation of Zika virus diagnosis, prevention, and management guidelines in Colombia, and to characterize their influence on efforts to defend sexual and reproductive rights. METHODS: A qualitative study performed between February and April 2018 in three municipalities in Colombia. We conducted 30 semistructured interviews and five focus groups with key informants who played a role during the epidemic. These included decision-makers, program coordinators, healthcare providers, pregnant women diagnosed with Zika virus, and members of affected communities. RESULTS: We identified barriers to and facilitators for the implementation of the national Zika virus response plan. Barriers included a lack of coordination between vector control efforts and in the realms of sexual and reproductive rights. Facilitators included healthcare providers' response to the epidemic, the development of technical skills, and the establishment of coordination and referral networks across different institutions. CONCLUSION: A multidimensional approach that considers healthcare services, gender issues, and the environment is crucial. We highlight the epidemic's effects on women's sexual and reproductive rights, mainly related to inequalities in sexual and reproductive health such as the increased risk of sexually transmitted infections experienced by the poorest and most vulnerable women.

17.
Bioorg Med Chem Lett ; 30(4): 126897, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31882298

RESUMO

The nucleoside/nucleotide derived antiviral agents have been the most important components of antiviral therapy used in clinics. Recently, the focus of the medicinal chemists within this exciting research field has been affected mainly by the lack of effective therapies for the Hepatitis C virus (HCV) infection and several other "neglected" diseases caused by viruses such as Zika or Dengue. 2'-Methyl modified nucleosides and their monophosphate prodrugs (ProTides) have revolutionized the therapies for HCV in the last few years and, according to the latest research efforts, have also brought a promise for treatment of diseases caused by other members of Flaviviridae family. Here, we report on the design and synthesis of 5'-N and S modified ProTides derived from 2'-methyladenosine. We studied potential applicability of these derivatives as prodrugs of this archetypal antiviral compound.

18.
Eur J Med Chem ; 187: 111956, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31841728

RESUMO

We have reported on aristeromycin (1) and 6'-fluorinated-aristeromycin analogues (2), which are active against RNA viruses such as Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus (ZIKV), and Chikungunya virus (CHIKV). However, these exhibit substantial cytotoxicity. As this cytotoxicity may be attributed to 5'-phosphorylation, we designed and synthesized one-carbon homologated 6'-fluorinated-aristeromycin analogues. This modification prevents 5'-phosphorlyation by cellular kinases, whereas the inhibitory activity towards S-adenosyl-l-homocysteine (SAH) hydrolase will be retained. The enantiomerically pure 6'-fluorinated-5'-homoaristeromycin analogues 3a-e were synthesized via the electrophilic fluorination of the silyl enol ether with Selectfluor, using a base-build up approach as the key steps. All synthesized compounds exhibited potent inhibitory activity towards SAH hydrolase, among which 6'-ß-fluoroadenosine analogue 3a was the most potent (IC50 = 0.36 µM). Among the compounds tested, 6'-ß-fluoro-homoaristeromycin 3a showed potent antiviral activity (EC50 = 0.12 µM) against the CHIKV, without noticeable cytotoxicity up to 250 µM. Only 3a displayed anti-CHIKV activity, whereas both3a and 3b inhibited SAH hydrolase with similar IC50 values (0.36 and 0.37 µM, respectively), which suggested that 3a's antiviral activity did not merely depend on the inhibition of SAH hydrolase. This is further supported by the fact that the antiviral effect was specific for CHIKV and some other alphaviruses and none of the homologated analogues inhibited other RNA viruses, such as SARS-CoV, MERS-CoV, and ZIKV. The potent inhibition and high selectivity index make 6'-ß-fluoro-homoaristeromycin (3a) a promising new template for the development of antivirals against CHIKV, a serious re-emerging pathogen that has infected millions of people over the past 15 years.

19.
Nat Commun ; 10(1): 5677, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831806

RESUMO

An important goal of the Zika virus (ZIKV) vaccine is to prevent a congenital syndrome in fetuses of pregnant women, but studies directly evaluating maternal vaccination for ZIKV are lacking. Here we report maternal vaccination using a live-attenuated ZIKV vaccine (3'UTR-∆10-LAV) in a pregnant mouse model. Maternal immunization with 3'UTR-∆10-LAV does not cause any adverse effects on pregnancy, fetal development, or offspring behavior. One maternal immunization fully protects dams against ZIKV infection and in utero transmission. Although neutralizing antibody alone is sufficient to prevent in utero transmission, a higher neutralizing titer is required to protect pregnant mice against in utero transmission than that required to protect non-pregnant mice against viral infection. The immunized dams transfer maternal antibodies to pups, which protect neonates against ZIKV infection. Notably, pregnancy weakens maternal T cell response to 3'UTR-∆10-LAV vaccination. Our results suggest that, besides vaccinating non-pregnant individuals, 3'UTR-∆10-LAV may also be considered for maternal vaccination.

20.
Semin Pediatr Neurol ; 32: 100769, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31813517

RESUMO

This review includes the congenital infections best known by the acronym TORCH (Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes virus), as well as Zika virus infection and perinatally acquired infections (enterovirus, parechovirus, rotavirus, parvovirus). Congenital infections are due to pathogens that can cross the placenta and are more likely to injure the brain when the infection occurs early in pregnancy. There are many similarities, with regards to brain lesions, for congenital Zika syndrome and congenital cytomegalovirus infection. Perinatally acquired viral infections tend to injure the white matter, with cystic evolution being more likely in the (late) preterm infant compared to the full-term infant. Congenital and perinatally acquired viral infections can be associated with adverse neurological outcomes. Prevention is important, especially as therapeutic options are limited. In this review both congenital as well as perinatally acquired viral infections will be discussed with a focus on neuro-imaging findings.

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