Zika Virus Research Articles

The NS2B-PP1α-eIF2α axis: Inhibiting stress granule formation and Boosting Zika virus replication.

Stress granules (SGs), formed by untranslated messenger ribonucleoproteins (mRNPs) during cellular stress in eukaryotes, have been linked to flavivirus interference without clear understanding. This study reveals the role of Zika virus (ZIKV) NS2B as a scaffold protein mediating interaction between protein phosphatase 1α (PP1α) and eukaryotic initiation factor 2α (eIF2α). This interaction promotes eIF2α dephosphorylation by PP1α, inhibiting SG formation. The NS2B-PP1α complex exhibits remarkable stability, resisting ubiquitin-induced degradation and amplifying eIF2α dephosphorylation, thus promoting ZIKV replication. In contrast, the NS2BV35A mutant, interacting exclusively with eIF2α, fails to inhibit SG formation, resulting in reduced viral replication and diminished impact on brain organoid growth. These findings reveal PP1α's dual role in ZIKV infection, inducing interferon production as an antiviral factor and suppressing SG formation as a viral promoter. Moreover, we found that NS2B also serves as a versatile mechanism employed by flaviviruses to counter host antiviral defenses, primarily by broadly inhibiting SG formation. This research advances our comprehension of the complex interplay in flavivirus-host interactions, offering potential for innovative therapeutic strategies against flavivirus infections.

Neurodevelopmental Outcomes of Preschoolers with Antenatal Zika Virus Exposure Born in the United States.

Neurodevelopmental outcomes for preschool-age children in the United States with in utero Zika virus (ZIKV) exposure have not yet been reported. We performed a case-control study to assess whether children exposed in utero to ZIKV have abnormal neurodevelopment at age 4-5 years compared to unexposed controls. Thirteen ZIKV-exposed cases that did not have microcephaly or other specific features of congenital Zika syndrome and 12 controls were evaluated between ages 4-5 years. Child neurodevelopment was assessed using the Pediatric Evaluation of Disability Inventory, Behavior Rating Inventory of Executive Function, Peabody Picture Vocabulary Test, Bracken School Readiness Assessment (BSRA), and Movement Assessment Battery for Children (MABC). Caregivers answered questions on the child's medical history and family demographics. Cases and controls were evaluated at mean (SD) ages 4.9 (0.3) and 4.8 (0.4) years, respectively. Caregivers reported more behavior and mood problems in cases than controls. MABC scores showed more gross and fine motor coordination difficulties among cases than controls. Controls trended towards higher performance on concepts underlying school readiness on BSRA. Three cases had a diagnosis of autism spectrum disorder or global developmental delay. Continued follow-up through school age for children with prenatal ZIKV exposure is needed to understand the impact of in utero ZIKV exposure on motor coordination, cognition, executive function, and academic achievement.

Evolution of STAT2 resistance to flavivirus NS5 occurred multiple times despite genetic constraints

Zika and dengue virus nonstructural protein 5 antagonism of STAT2, a critical interferon signaling transcription factor, to suppress the host interferon response is required for viremia and pathogenesis in a vertebrate host. This affects viral species tropism, as mouse STAT2 resistance renders only immunocompromised or humanized STAT2 mice infectable. Here, we explore how STAT2 evolution impacts antagonism. By measuring the susceptibility of 38 diverse STAT2 proteins, we demonstrate that resistance arose numerous times in mammalian evolution. In four species, resistance requires distinct sets of multiple amino acid changes that often individually disrupt STAT2 signaling. This reflects an evolutionary ridge where progressive resistance is balanced by the need to maintain STAT2 function. Furthermore, resistance may come with a fitness cost, as resistance that arose early in lemur evolution was subsequently lost in some lemur lineages. These findings underscore that while it is possible to evolve resistance to antagonism, complex evolutionary trajectories are required to avoid detrimental host fitness consequences.

Structure of an RNA G-quadruplex from the West Nile virus genome

Potential G-quadruplex sites have been identified in the genomes of DNA and RNA viruses and proposed as regulatory elements. The genus Orthoflavivirus contains arthropod-transmitted, positive-sense, single-stranded RNA viruses that cause significant human disease globally. Computational studies have identified multiple potential G-quadruplex sites that are conserved across members of this genus. Subsequent biophysical studies established that some G-quadruplexes predicted in Zika and tickborne encephalitis virus genomes can form and known quadruplex binders reduced viral yields from cells infected with these viruses. The susceptibility of RNA to degradation and the variability of loop regions have made structure determination challenging. Despite these difficulties, we report a high-resolution structure of the NS5-B quadruplex from the West Nile virus genome. Analysis reveals two stacked tetrads that are further stabilized by a stacked triad and transient noncanonical base pairing. This structure expands the landscape of solved RNA quadruplex structures and demonstrates the diversity and complexity of biological quadruplexes. We anticipate that the availability of this structure will assist in solving further viral RNA quadruplexes and provides a model for a conserved antiviral target in Orthoflavivirus genomes.

Zika virus non-coding RNAs antagonize antiviral responses by PKR-mediated translational arrest.

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that causes severe outbreaks in human populations. ZIKV infection leads to the accumulation of small non-coding viral RNAs (known as sfRNAs) that are crucial for evasion of antiviral responses and for viral pathogenesis. However, the mechanistic understanding of how sfRNAs function remains incomplete. Here, we use recombinant ZIKVs and ribosome profiling of infected human cells to show that sfRNAs block translation of antiviral genes. Mechanistically, we demonstrate that specific RNA structures present in sfRNAs trigger PKR activation, which instead of limiting viral replication, enhances viral particle production. Although ZIKV infection induces mRNA expression of antiviral genes, translation efficiency of type I interferon and interferon stimulated genes were significantly downregulated by PKR activation. Our results reveal a novel viral adaptation mechanism mediated by sfRNAs, where ZIKV increases its fitness by repurposing the antiviral role of PKR into a proviral factor.

In silico screening for potential inhibitors from the phytocompounds of Carica papaya against Zika virus NS5 protein.

The Zika virus (ZIKV) infection has emerged as a global health threat. The causal reasoning is that Zika infection is linked to the development of microcephaly in newborns and Guillain-Barré syndrome in adults. With no clinically approved antiviral treatment for ZIKV, the need for the development of potential inhibitors against the virus is essential. In this study, we aimed to screen phytochemicals from papaya ( Carica papaya L.) against NS5 protein domains of ZIKV. Approximately 193 phytochemicals from an online database (IMPACT) were subjected to molecular docking using AutoDock Vina against the NS5-MTase protein domain (5WXB) and -RdRp domain (5U04). Our results showed that β-sitosterol, carpaine, violaxanthin, pseudocarpaine, Δ7-avenasterols, Rutin, and cis-β-carotene had the highest binding affinity to both protein domains, with β-sitosterol having the most favorable binding energy. Furthermore, ADMET analysis revealed that selected compounds had good pharmacokinetic properties and were nontoxic. Our findings suggest that papaya-derived phytochemicals could be potential candidates for developing antiviral drugs against ZIKV. However, further experimental studies using cell lines and in vivo models are needed to validate their efficacy and safety.

Aedes albopictus saliva contains a richer microbial community than the midgut

BackgroundPast findings demonstrate that arthropods can egest midgut microbiota into the host skin leading to dual colonization of the vertebrate host with pathogens and saliva microbiome. A knowledge gap exists on how the saliva microbiome interacts with the pathogen in the saliva. To fill this gap, we need to first define the microbial composition of mosquito saliva.MethodsThe current study aimed at analyzing and comparing the microbial profile of Aedes albopictus saliva and midgut as well as assessing the impact of Zika virus (ZIKV) infection on the midgut and saliva microbial composition. Colony-reared Ae. albopictus strains were either exposed to ZIKV infectious or noninfectious bloodmeal. At 14 ays postinfection, the 16S V3–V4 hypervariable rRNA region was amplified from midgut and saliva samples and sequenced on an Illumina MiSeq platform. The relative abundance and diversity of midgut and saliva microbial taxa were assessed.ResultsWe observed a richer microbial community in the saliva compared with the midgut, yet some of the microbial taxa were common in the midgut and saliva. ZIKV infection did not impact the microbial diversity of midgut or saliva. Further, we identified Elizabethkingia spp. in the Ae. albopictus saliva.ConclusionsThis study provides insights into the microbial community of the Ae. albopictus saliva as well as the influence of ZIKV infection on the microbial composition of its midgut and saliva. The identification of Elizabethkingia spp., an emerging pathogen of global health significance, in Ae. albopictus saliva is of medical importance. Future studies to assess the interactions between Ae. albopictus saliva microbiome and ZIKV could lead to novel strategies for developing transmission barrier tools.Graphical

Chemically Peptide Synthesis and Role of Arginine and Lysine in the Antimicrobial and Antiviral Activity of Synthetic Peptides: A Comprehensive Review

ABSTRACTThis review examines the potential applications of peptides in biotechnology, medicine, and pharmacy, while highlighting the important antibacterial and antiviral properties of peptides. Peptides and chemical peptide synthesis have become a field of study that is gaining great momentum today. Some of the main reasons for this are high specificity, biodegradability and versatility of peptides. Peptides also have some specific properties that make them attractive for pharmaceutical development. As a case study, it can be used to create peptides that can be used to replace or fix damaged proteins in the body by mimicking the action of naturally occurring proteins. Delivering drugs or other therapeutic agents to specific cells or tissues is another method that can help increase the effectiveness of treatment and reduce unwanted effects. Various types of antimicrobial peptides (AMPs), such as defensins and cathelicidins, and their anti‐infective properties are also discussed. Finally, peptides (melittin, lactoferricin, etc.) can be used to trigger an immune response against certain infections, such as COVID‐19 and Zika virus, by acting as vaccines. In our study, a comprehensive review was made on antiviral and AMPs, and especially peptides containing arginine and lysine were mentioned. The properties of these peptides, examples of these peptides and their developments in the pharmaceutical field are emphasized.

Association between Sleep and Language Development in Children with Congenital Zika Syndrome.

Congenital Zika Virus Syndrome (CZS) presents notable hurdles to neurodevelopment, with language development emerging as a crucial aspect. This study investigates sleep patterns and language skills in children with CZS, aiming to explore the potential synchronization of sleep development with their neurodevelopment. We studied cross-sectionally 135 children with CZS aged 0 to 48 months, investigating sleep using the BISQ Questionnaire. Language development was assessed using the Early Language Milestone Scale, while motor development and cognitive and social ability were assessed using the Bayley Scales of Infant and Young Child Development 3rd edition. We also studied longitudinally a cohort of 16 children (initially aged 0 to 12 months) whom we followed for four years, assessing at one-year intervals. Sleep disturbances and language deficits were highly frequent in this population. In the 0-12 months group, a late bedtime and frequent nighttime awakenings were associated with poorer auditory expressive skills. At 13-24 months, nighttime awakenings were associated with poorer auditory expressive skills, while among 25-36-month-olds decreased auditory receptive skills were associated with longer sleep onset latency and reduced nighttime sleep duration. The brain alterations caused by Zika virus infection affect both sleep disturbances and delays in language development. It is possible that sleep disturbance may be a mediating factor in the pathway between CZS and delayed language development, as the three analyzed language skills showed a correlation with sleep parameters.

Zika virus exists in enterocytes and enteroendocrine cells of the Aedes aegypti midgut

The Aedes aegypti midgut is crucial for blood digestion, nutrition, reproduction, and pathogen interaction. Using single-cell RNA sequencing, we explored virus infection and transcriptomic changes at the cellular level. We identified 12 distinct cell clusters in the Ae. aegypti midgut post-Zika virus infection, including intestinal stem cells, enteroblasts, enteroendocrine cells (EE), and enterocytes (ECs). The virus was found mainly in specific subsets of ECs and EE. Infection altered transcriptional profiles related to metabolism, signaling, and immune responses. Functional studies highlighted three significantly differentially expressed genes in infected cells. Notably, silencing apolipophorin III reduced virus RNA copy number in the midgut, emphasizing the role of specific genes in viral infection. These findings enhance our understanding of mosquito midgut cell processes during Zika virus infection and suggest potential targets for vector control.

Glasgow's fight against climate change

Prof. Malcolm Shepherd’s introduction inour December 23’ issue highlighted thatclimate change is an extremely importanttopic which merits further coverage inSurgo. With the guidance and knowledge ofDr. Camille Huser (recently appointedDeputy Director of the UndergraduateMedical School (Bioscience)), I was able toexplore this topic and understand our role asa medical school in the fight against climatechange. Climate change will continue to become anenormous burden on healthcare. However,healthcare plays an alarming role inaccelerating climate change. Today’s warmerclimates have seen an increase in globaldroughts, floods and heatwaves. They allowwater and food borne diseases to thrive andvectors carrying fatal illnesses such asmalaria, dengue fever and zika virus tosurvive at higher altitudes and for longerperiods of time. In fact, eggs of the nonnative aedes albopictus mosquito (known totransmit both dengue fever and zika virus!)have been found in the UK within recentyears. However, it isn’t just so-called“tropical diseases” we need to consider. Warmer summers are altering our airquality, causing prolonged periods of highpollen that can amplify the number ofasthma exacerbation and allergic reactioncases that we see coming through ourhospital doors each year. Est. 1935Climate change is deadly. I was alarmed toread that the UK government predicts thatby 2070 there will be a 1244% rise inheatwave related deaths; unfortunately andunjustly affecting economically and sociallymarginalised individuals the most. (1, 2)You may be thinking we will have our workcut out as future clinicians, taking on theburden of climate change. However, we alsoface the large task of trying to limit ourcontribution to global warming as clinicians.The faculty of Public Health estimates thatinternationally, healthcare accounts for 4.4%of global net emissions (that is more thanaviation!). Although, it is not all doom andgloom as our requirement to do better hasbeen identified and NHS Scotland aims tohave a net 0 carbon footprint by 2040.Already, there have been improvementsfrom NHS GGC: reduced desflurane usage inanesthetics, opting for powdered/soft mist inhalers and minimizing SABA usage,encouraging staff to use sustainabletransport methods to travel to work andpurchasing products and services fromsuppliers aligned with the net 0commitments. (3, 4)But what are we doing as a medical school? Imet with Camille to find out more. In linewith the sustainability requirements of GMCgood medical practice (January 2024), theMedical Schools Council (MSC) havehighlighted the need to incorporatesustainability into the MBChB curriculum.Glasgow University were key in coordinatingan MSC network of 38+ UK medical schools,aiming to facilitate sharing of expertise andresources. Dr. Noy Basu (lead of the verticaltheme: Global and planetary health) hasbeen key to delivering these changes inGlasgow after a survey of our medicalstudents revealed that >90% wantedsustainable healthcare to feature in thecurriculum. Now, sustainability in healthcareappears in assessment, lectures and SSCopportunities, particularly in years 1 and 2.Camille acknowledged that a key drivingforce behind improvement is students. Everyyear, students have grouped together tocomplete the planetary health report card(PHRC): a tool for evaluating and improving planetary health content in healthprofessional schools. Furthermore, we havea global goals student group who collaborateand focus on ways in which we can alter ourbehavior to achieve the United Nationssustainable development goals by 2030(which largely consider the environment andclimate change). Glasgow University is alsopart of Universitas 21 (U21): a global networkof universities that aims to connect studentsand staff. They have a subgroup (thesustainable development group) with ashared commitment to fighting climatechange. I asked Camille about ways in which we couldstill do more. She believes progress can bemade through engaging and educating staff;as it is every lecturers’ job when teachingstudents to incorporate sustainablehealthcare into the curriculum.Furthermore, continued partnership withstudents is essential in cultivating new ideassurrounding this topic. If you have ideas asto how we can combat climate change as amedical school or, if would like to getinvolved with some of the student groupsmentioned above, please contact Camille(Camille.Huser@glasgow.ac.uk). It is our job as clinicians of tomorrow topractice sustainably. Lots of progress hasbeen made to reach NHS targets but there isstill so much to be done. - Anna, Editor inChief. Further reading:Breaking the Feverreport_0.pdf

Genetic diversity of Flaviviridae and Rhabdoviridae EVEs in Aedes aegypti and Aedes albopictus on Hainan Island and the Leizhou Peninsula, China

BackgroundHainan Island and the Leizhou Peninsula, the southernmost part of mainland China, are areas where Aedes aegypti and Ae. albopictus are sympatric and are also high-incidence areas of dengue outbreaks in China. Many studies have suggested that Aedes endogenous viral components (EVEs) are enriched in piRNA clusters which can silence incoming viral genomes. Investigation the EVEs present in the piRNA clusters associated with viral infection of Aedes mosquitoes in these regions may provide a theoretical basis for novel transmission-blocking vector control strategies. MethodsIn this study, specific primers for endogenous Flaviviridae elements (EFVEs) and endogenous Rhabdoviridae elements (ERVEs) were used to detect the distribution of Zika virus infection associated EVEs in the genomes of individuals of the two Aedes mosquitoes. Genetic diversity of EVEs with a high detection rate was also analyzed. ResultsThe results showed that many EVEs associated with Zika virus infection were detected in both Aedes species, with the detection rates were 47.68% to 100% in Ae. aegypti and 36.15% to 92.31% in sympatric Ae. albopictus populations. EVEs detection rates in another 17 Ae. albopictus populations ranged from 29.39% to 89.85%. Genetic diversity analyses of the four EVEs (AaFlavi53, AaRha61, AaRha91 and AaRha100) of Ae. aegypti showed that each had high haplotype diversity and low nucleotide diversity. The number of haplotypes in AaFlavi53 was 8, with the dominant haplotype being Hap_1 and the other 7 haplotypes being further mutated from Hap_1 in a lineage direction. In contrast, the haplotype diversity of the other three ERVEs (AaRha61, AaRha91 and AaRha100) was more diverse and richer, with the haplotype numbers were 9, 15 and 19 respectively. In addition, these EVEs all showed inconsistent patterns of both population differentiation and dispersal compared to neutral evolutionary genes such as the Mitochondrial COI gene. ConclusionThe EFVEs and ERVEs tested were present at high frequencies in the field Aedes mosquito populations. The haplotype diversity of the EFVE AaFlavi53 was relatively lower and the three ERVEs (AaRha61, AaRha91, AaRha100) were higher. None of the four EVEs could be indicative of the genetic diversity of the Ae. aegypti population. This study provided theoretical support for the use of EVEs to block arbovirus transmission, but further research is needed into the mechanisms by which these EVEs are antiviral to Aedes mosquitoes.

Regulatory T cells restrict immunity and pathology in distal tissue sites following a localized infection

Regulatory T cells (Tregs) are well-known to mediate peripheral tolerance at homeostasis, and there is a growing appreciation for their role in modulating infectious disease immunity. Following acute and chronic infections, Tregs can restrict pathogen-specific T cell responses to limit immunopathology. However, it is unclear if Tregs mediate control of pathology and immunity in distal tissue sites during localized infections. We investigated the role of Tregs in immunity and disease in various tissue compartments in the context of “mild” vaginal Zika virus infection. We found that Tregs are critical to generating robust virus-specific CD8 T cell responses in the initial infection site. Further, Tregs limit inflammatory cytokines and immunopathology during localized infection; a dysregulated immune response in Treg-depleted mice leads to increased T cell infiltrates and immunopathology in both the vagina and the central nervous system (CNS). Importantly, these CNS infiltrates are not present at the same magnitude during infection of Treg-sufficient mice, in which there is no CNS immunopathology. Our data suggest that Tregs are necessary to generate a robust virus-specific response at the mucosal site of infection, while Treg-mediated restriction of bystander inflammation limits immunopathology both at the site of infection as well as distal tissue sites.

Zika virus replication is impaired by a selective agonist of the TRPML2 ion channel

The flavivirus genus includes human pathogenic viruses such as Dengue (DENV), West Nile (WNV) and Zika virus (ZIKV) posing a global health threat due to limited treatment options. Host ion channels are crucial for various viral life cycle stages, but their potential as targets for antivirals is often not fully realized due to the lack of selective modulators. Here, we observe that treatment with ML2-SA1, an agonist for the human endolysosomal cation channel TRPML2, impairs ZIKV replication. Upon ML2-SA1 treatment, levels of intracellular genomes and number of released virus particles of two different ZIKV isolates were significantly reduced and cells displayed enlarged vesicular structures and multivesicular bodies with ZIKV envelope protein accumulation. However, no increased ZIKV degradation in lysosomal compartments was observed. Rather, the antiviral effect of ML2-SA1 seemed to manifest by the compound’s negative impact on genome replication. Moreover, ML2-SA1 treatment also led to intracellular cholesterol accumulation. ZIKV and many other viruses including the Orthohepevirus Hepatitis E virus (HEV) rely on the endolysosomal system and are affected by intracellular cholesterol levels to complete their life cycle. Since we observed that ML2-SA1 also negatively impacted HEV infections in vitro, this compound may harbor a broader antiviral potential through perturbing the intracellular cholesterol distribution. Besides indicating that TRPML2 may be a promising target for combatting viral infections, we uncover a tentative connection between this protein and cholesterol distribution within the context of infectious diseases.

Novel quinoline substituted autophagy inhibitors attenuate Zika virus replication in ocular cells

Zika virus (ZIKV) is a re-emerging RNA virus that is known to cause ocular and neurological abnormalities in infants. ZIKV exploits autophagic processes in infected cells to enhance its replication and spread. Thus, autophagy inhibitors have emerged as a potent therapeutic target to combat RNA viruses, with Hydroxychloroquine (HCQ) being one of the most promising candidates. In this study, we synthesized several novel small-molecule quinoline derivatives, assessed their antiviral activity, and determined the underlying molecular mechanisms. Among the nine synthesized analogs, two lead candidates, labeled GL-287 and GL-382, significantly attenuated ZIKV replication in human ocular cells, primarily by inhibiting autophagy. These two compounds surpassed the antiviral efficacy of HCQ and other existing autophagy inhibitors, such as ROC-325, DC661, and GNS561. Moreover, unlike HCQ, these novel analogs did not exhibit cytotoxicity in the ocular cells. Treatment with compounds GL-287 and GL-382 in ZIKV-infected cells increased the abundance of LC3 puncta, indicating the disruption of the autophagic process. Furthermore, compounds GL-287 and GL-382 effectively inhibited the ZIKV-induced innate inflammatory response in ocular cells. Collectively, our study demonstrates the safe and potent antiviral activity of novel autophagy inhibitors against ZIKV.

The neuroepidemiological and social risks in neonates related to the Zika virus

Introdução: Entre os anos de 2015 e 2016, o Brasil apresentou um aumento de casos de microcefalia em neonatos, durante uma epidemia de Zika Vírus (ZIKV) - um Flavivírus descoberto em 1947 na floresta de Zika, Uganda. Durante esse período foi confirmada a relação entre a contaminação por ZIKV na gestação e alterações cerebrais congênitas graves em recém-nascidos. As consequências de tal correlação foram profundas, afetando famílias e comunidades e exigindo uma mobilização significativa de recursos e apoio para os cuidados e desenvolvimento das crianças afetadas. Objetivo: O objetivo geral deste estudo é associar a infecção pelo ZIKV com os distúrbios congênitos neurológicos. Metodologia: Consiste em revisão analítica de literatura, realizada a partir de artigos científicos e base de dados de parâmetros seguros, tais quais SciELO, PubMed, Google Acadêmico e Ministério da Saúde. Além de uma visita técnica para um embasamento científico com uma profissional da área, bem como uma intervenção social, desenvolvida para orientação de gestantes, por meio de um folder informativo. Desenvolvimento: Dentre os riscos neurológicos, deletérios ao feto durante o desenvolvimento, a microcefalia mostrou-se o sinal mais evidenciado entre as crianças afetadas, relacionando-se à capacidade de disseminação transplacentária e ao mecanismo apoptótico das células embrionárias. Entre a população atingida, observou-se maior incidência na região Nordeste, entre mães solteiras, com idade maior que 30 anos, baixa escolaridade, autodeclaradas negras, de baixa renda e residentes em áreas com menor cobertura em políticas públicas. Ademais, entre os desfechos, o óbito entre os neonatos atingidos teve média de 1,4 meses, além de prematuridade e baixo peso ao nascer, relacionando condições nutricionais e de saúde com fatores sociais. Por mais, notabilizou-se que a obtenção de alterações em neonatos, por vezes, foi evidenciada somente após o nascimento e o diagnóstico fora dificultado no início epidêmico. Entretanto, o impacto no enfrentamento mostrou-se integral não somente para as crianças, mas às famílias atingidas, evidenciando a necessidade do amparo e a imperiosidade de ações educativas voltadas à proteção contra o vírus. Considerações finais: Pelo exposto, concluiu-se que os riscos neurológicos em neonatos decorrentes do ZIKV estiveram associados a uma tríade de aspectos: as condições sociodemográficas e ambientais facilitaram a disseminação rápida do vírus notadamente entre a população com maiores vulnerabilidades sociais, desencadeando danos neurológicos aos fetos em desenvolvimento, maiores no primeiro trimestre da gestação. A prevenção destaca-se como uma das formas mais importantes de ação em saúde no combate à proliferação desse vírus.

Disruption of myelin structure and oligodendrocyte maturation in a macaque model of congenital Zika infection

Zika virus (ZikV) infection during pregnancy can cause congenital Zika syndrome (CZS) and neurodevelopmental delay in infants, of which the pathogenesis remains poorly understood. We utilize an established female pigtail macaque maternal-to-fetal ZikV infection/exposure model to study fetal brain pathophysiology of CZS manifesting from ZikV exposure in utero. We find prenatal ZikV exposure leads to profound disruption of fetal myelin, with extensive downregulation in gene expression for key components of oligodendrocyte maturation and myelin production. Immunohistochemical analyses reveal marked decreases in myelin basic protein intensity and myelinated fiber density in ZikV-exposed animals. At the ultrastructural level, the myelin sheath in ZikV-exposed animals shows multi-focal decompaction, occurring concomitant with dysregulation of oligodendrocyte gene expression and maturation. These findings define fetal neuropathological profiles of ZikV-linked brain injury underlying CZS resulting from ZikV exposure in utero. Because myelin is critical for cortical development, ZikV-related perturbations in oligodendrocyte function may have long-term consequences on childhood neurodevelopment, even in the absence of overt microcephaly.

CD8+ T cells promote ZIKV clearance and mitigate testicular damage in mice

Zika virus (ZIKV) causes human testicular inflammation and alterations in sperm parameters and causes testicular damage in mouse models. The involvement of individual immune cells in testicular damage is not fully understood. We detected virus in the testes of the interferon (IFN) α/β receptor−/− A129 mice three weeks post-infection and found elevated chemokines in the testes, suggesting chronic inflammation and long-term infection play a role in testicular damage. In the testes, myeloid cells and CD4+ T cells were absent at 7 dpi but were present at 23 days post-infection (dpi), and CD8+ T cell infiltration started at 7 dpi. CD8−/− mice with an antibody-depleted IFN response had a significant reduction in spermatogenesis, indicating that CD8+ T cells are essential to prevent testicular damage during long-term ZIKV infections. Our findings on the dynamics of testicular immune cells and the importance of CD8+ T cells function as a framework to understand mechanisms underlying observed inflammation and sperm alterations in humans.

EPH176 Comparison of Superoxide Dismutase Activities (Mn-SOD AND Cu/Zn-SOD) in Patients Infected with Dengue Virus or Zika Virus

EPH176 Comparison of Superoxide Dismutase Activities (Mn-SOD AND Cu/Zn-SOD) in Patients Infected with Dengue Virus or Zika Virus

Seroprevalence of Zika virus in pregnant women in Brazil: a cohort study in the macroregion of Dourados - Mato Grosso do Sul

Seroprevalence of Zika virus in pregnant women in Brazil: a cohort study in the macroregion of Dourados - Mato Grosso do Sul