Sustained Microglial Activation Promotes Synaptic Loss and Neuronal Dysfunction after Recovery from ZIKV Infection.

Zika virus (ZIKV), transmitted by Aedes mosquitoes, has been a global health concern since 2007. It primarily causes fetal microcephaly and neuronal defects through maternal transmission and induces neurological complications in adults. Recent studies report elevated proinflammatory cytokines and persistent neurological alterations post recovery, but the in vivo mechanisms remain unclear. In our study, viral RNA loads in the brains of mice infected with ZIKV peaked at 7 days post infection and returned to baseline by day 21, indicating recovery. RNA sequencing of the cerebral cortex at 7 and 21 days revealed upregulated genes related to neuroinflammation and microglial activation. Histological analyses indicated neuronal cell death and altered neurite morphology owing to severe neuroinflammation. Additionally, sustained microglial activation was associated with increased phospho-Tau levels, constituting a marker of neurodegeneration. These findings highlight how persistent microglial activation leads to neuronal dysfunction post ZIKV recovery, providing insights into the molecular pathogenesis of ZIKV-induced brain abnormalities.

Fetal Zika virus inoculation in macaques revealed control of the fetal viral load during pregnancy.

BACKGROUND: Early pregnancy Zika virus (ZIKV) infection is associated with major brain damage in fetuses, leading to microcephaly in 0.6-5.0% of cases, but the underlying mechanisms remain largely unknown. METHODS: To understand the kinetics of ZIKV infection during fetal development in a nonhuman primate model, four cynomolgus macaque fetuses were exposed in utero through echo-guided intramuscular inoculation with 103 PFU of ZIKV at 70-80 days of gestation, 2 controls were mock inoculated. Clinical, immuno-virological and ultrasound imaging follow-ups of the mother/fetus pairs were performed until autopsy after cesarean section 1 or 2 months after exposure (n = 3 per group). RESULTS: ZIKV was transmitted from the fetus to the mother and then replicate in the peripheral blood of the mother from week 1 to 4 postexposure. Infected fetal brains tended to be smaller than those of controls, but not the femur lengths. High level of viral RNA ws found after the first month in brain tissues and placenta. Thereafter, there was partial control of the virus in the fetus, resulting in a decreased number of infected tissue sections and a decreased viral load. Immune cellular and humoral responses were effectively induced. CONCLUSIONS: ZIKV infection during the second trimester of gestation induces short-term brain injury, and although viral genomes persist in tissues, most of the virus is cleared before delivery.

Boletim epidemiológico: monitoramento dos casos de arboviroses em Goiás da semana epidemiológica 01 a 33 de 2024 / Epidemiological bulletin: monitoring of arbovirus cases in Goiás from epidemiological week 01 to 33 of 2024

As arboviroses transmitidas pelo mosquito Aedes aegypt são um dos principais problemas de saúde pública no Estado de Goiás. O boletim epidemiológico das arboiross tem o objetivo de apresentar a situação epidemiológica dos casos no estado, utilizando como fonte de dados os registros de casos suspeitos e confirmados ocorridos nos últimos anos, disponíveis no SINan Online e SINAN Net também são apresentados dados relativos à síndrome congênita associada à infecção peli Zika vírus, disponíveis no Sistema de Registro de Eventos em Saúde Pública (RESP) - Microcefalias

Arboviruses transmitted by the Aedes aegypt mosquito are one of the main public health problems in the State of Goiás. The arboiross epidemiological bulletin aims to present the epidemiological situation of cases in the state, using records of suspected and confirmed cases as a data source. occurred in recent years, available on SINan Online and SINAN Net, data relating to congenital syndrome associated with Zika virus infection, available on the Public Health Event Registration System (RESP) - Microcephaly, is also presented

Zika virus vertical transmission induces neuroinflammation and synapse impairment in brain cells derived from children born with Congenital Zika Syndrome.

Zika virus (ZIKV) infection was first reported in 2015 in Brazil as causing microcephaly and other developmental abnormalities in newborns, leading to the identification of Congenital Zika Syndrome (CZS). Viral infections have been considered an environmental risk factor for neurodevelopmental disorders outcome, such as Autism Spectrum Disorder (ASD). Moreover, not only the infection per se, but maternal immune system activation during pregnancy, has been linked to fetal neurodevelopmental disorders. To understand the impact of ZIKV vertical infection on brain development, we derived induced pluripotent stem cells (iPSC) from Brazilian children born with CZS, some of the patients also being diagnosed with ASD. Comparing iPSC-derived neurons from CZS with a control group, we found lower levels of pre- and postsynaptic proteins and reduced functional synapses by puncta co-localization. Furthermore, neurons and astrocytes derived from the CZS group showed decreased glutamate levels. Additionally, the CZS group exhibited elevated levels of cytokine production, one of which being IL-6, already associated with the ASD phenotype. These preliminary findings suggest that ZIKV vertical infection may cause long-lasting disruptions in brain development during fetal stages, even in the absence of the virus after birth. These disruptions could contribute to neurodevelopmental disorders manifestations such as ASD. Our study contributes with novel knowledge of the CZS outcomes and paves the way for clinical validation and the development of potential interventions to mitigate the impact of ZIKV vertical infection on neurodevelopment.

Elucidating the inhibitory mechanism of Zika virus NS2B-NS3 protease with dipeptide inhibitors: Insights from molecular docking and molecular dynamics simulations.

Microcephaly, Guillain-Barré syndrome, and potential sexual transmission stand as prominent complications associated with Zika virus (ZIKV) infection. The absence of FDA-approved drugs or vaccines presents a substantial obstacle in combatting the virus. Furthermore, the inclusion of pregnancy in the pharmacological screening process complicates and extends the endeavor to ensure molecular safety and minimal toxicity. Given its pivotal role in viral assembly and maturation, the NS2B-NS3 viral protease emerges as a promising therapeutic target against ZIKV. In this context, a dipeptide inhibitor was specifically chosen as a control against 200 compounds for docking analysis. Subsequent molecular dynamics simulations extending over 200 ns were conducted to ascertain the stability of the docked complex and confirm the binding of the inhibitor at the protein's active site. The simulation outcomes exhibited conformity to acceptable thresholds, encompassing parameters such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), ligand-protein interaction analysis, ligand characterization, and surface area analysis. Notably, analysis of ligand angles bolstered the identification of prospective ligands capable of inhibiting viral protein activity and impeding virus dissemination. In this study, the integration of molecular docking and dynamics simulations has pinpointed the dipeptide inhibitor as a potential candidate ligand against ZIKV protease, thereby offering promise for therapeutic intervention against the virus.

[Zika virus infection: sexual transmission and implications for prevention]. / Infection au virus Zika: transmission sexuelle et conséquences sur la prévention: Présentation faite lors de la Journée scientifique de la SFMTSI du 9/11/2023 « Infections sexuellement transmissibles tropicales ¼.

Zika virus infection, most oft n responsible for a benign arboviral disease or an asymptomatic infection, rarely Guillain-Barré syndrome, can become problematic in pregnant women, due to a risk of fetal malformations, in particular microcephaly linked to its neurotropism. The most recent large-scale epidemic was observed throughout Latin America between 2015 and 2017, causing several hundred thousand cases. Transmission is predominantly vector-borne, but sexual transmission has been described, mainly among travelers, although it undoubtedly accounts for a significant proportion of transmission in epidemic areas. The aim of this review is to describe this sexual transmission, mainly through examples linked to this large-scale epidemic in Latin America, to describe the link with prolonged excretion of infectious viral particles in genital secretions, especially semen but also vaginal secretions, and to highlight possible preventive measures apart from vector transmission, in particular the need for pregnant women or women wishing to become pregnant to avoid visiting countries where circulation of Zika virus is described.

The inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in immunocompromised AG129 mice.

Zika virus, a mosquito-borne arbovirus, has repeatedly caused large pandemics with symptoms worsening from mild and self-limiting diseases to Guillain-Barré syndrome in adults and fetal microcephaly in newborns. In recent years, Zika virus diseases have posed a serious threat to human health. The shortage of susceptible small animal models makes it difficult to study pathogenic mechanisms and evaluate potential therapies for Zika virus infection. Therefore, we chose immunocompromised mice (AG129 mice) deficient in IFN-α/ß and IFN-γ receptors, which can abolish the innate immune system that prevents Zika virus infection early. AG129 mice were infected with the Zika virus, and this mouse model exhibited replication dynamics, tissue tropism, pathological lesion and immune activation of the Zika virus. Our results suggest that the inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in AG129 mice. By testing the potential antiviral drug favipiravir, several critical indicators, including replication dynamics and survival rates, were identified in AG129 mice after Zika virus infection. It is suggested that the model is reliable for drug evaluation. In brief, this model provides a potential platform for studies of the infectivity, virulence, and pathogenesis of the Zika virus. Moreover, the development of an accessible mouse model of Zika virus infection will expedite the research and deployment of therapeutics and vaccines.

MicroRNA profiles in Zika virus infection: Insights from diverse sources.

BACKGROUND: Zika virus (ZIKV) stands as one of the most significant reemerging viral pathogens, linked to neurological diseases such as meningoencephalitis and congenital microcephaly. Today there are no effective therapies for treating ZIKV-infected patients. MiRNAs play a critical role in regulating cellular signaling and physiological conditions, and alterations in their profiles can bear great significance in disease progression. OBJECTIVES: Despite significant progress in understanding the interaction between the ZIKV and its host since the outbreak, a more comprehensive understanding on these interactions is imperative. This review aims to summarize the studies in the field and shed light on the intricate relationship between ZIKV and its host at the molecular level. CONTENT: We found that in ZIKV-infected humans, over-expression of miR-431-5p and miR-30e-5p plays a crucial role in innate immune responses and contributes to neurological damage. Additionally, in ZIKA-infected mice, we observed upregulated expression of all the targets of miR-124-3p including CCL2, IL7, IRF1, and SBNO2. Notably, other targets of this miRNA include TLR6, TNF, STAT3, and NF-kB also exhibited upregulation in the central nervous system (CNS) of infected mice. Conversely, miR-654-3p levels were reduced, correlating with the upregulation of its predicted targets including FLT3LG, LITAF, CD69, and TLR2. In the case of insects, aae-miR-286a/b-3p was predicted to target all ZIKV genotypes. This specific miRNA is typically found in ovaries and can be transferred to embryos. In conclusion, our findings suggest that host microRNAs and ZIKV-encoded microRNAs hold promise as potential targets for the diagnosis of ZIKV infections and may even serve as a therapeutic approach for managing this infectious disease.

Zika virus capsid protein closed structure modulates binding to host lipid systems.

Zika virus (ZIKV), a mosquito-borne Flavivirus of international concern, causes congenital microcephaly in newborns and Guillain-Barré syndrome in adults. ZIKV capsid (C) protein, one of three key structural proteins, is essential for viral assembly and encapsidation. In dengue virus, a closely related flavivirus, the homologous C protein interacts with host lipid systems, namely intracellular lipid droplets, for successful viral replication. Here, we investigate ZIKV C interaction with host lipid systems, showing that it binds host lipid droplets but, contrary to expected, in an unspecific manner. Contrasting with other flaviviruses, ZIKV C also does not bind very-low density-lipoproteins. Comparing with other Flavivirus, capsid proteins show that ZIKV C structure is particularly thermostable and seems to be locked into an auto-inhibitory conformation due to a disordered N-terminal, hence blocking specific interactions and supporting the experimental differences observed. Such distinct structural features must be considered when targeting capsid proteins in drug development.

Integrative analysis of molecular pathways and morphological anomalies associated with congenital Zika syndrome.

Congenital Zika syndrome (CZS) comprises a set of clinical manifestations that can be presented by neonates born to mothers infected by the Zika virus (ZIKV). CZS-associated phenotypes include neurological, skeletal, and systemic alterations and long-term developmental sequelae. One of the most frequently reported clinical conditions is microcephaly characterized by a reduction in head circumference and cognitive complications. Nevertheless, the associations among the diverse signaling pathways underlying CZS phenotypes remain to be elucidated. To shed light on CZS, we have extensively reviewed the morphological anomalies resulting from ZIKV infection, as well as genes and proteins of interest obtained from the published literature. With this list of genes or proteins, we performed computational analyses to explore the cellular processes, molecular mechanisms, and molecular pathways related to ZIKV infection. Therefore, in this review, we comprehensively describe the morphological abnormalities caused by congenital ZIKV infection and, through the analysis noted above, propose common molecular pathways altered by ZIKV that could explain both central nervous system and craniofacial skeletal alterations.

Ad26.M.Env ZIKV vaccine protects pregnant rhesus macaques and fetuses against Zika virus infection.

At the start of the Zika virus (ZIKV) epidemic in 2015, ZIKV spread across South and Central America, and reached parts of the southern United States placing pregnant women at risk for fetal microcephaly, fetal loss, and other adverse pregnancy outcomes associated with congenital ZIKA syndrome (CZS). For this reason, testing of a safe and efficacious ZIKV vaccine remains a global health priority. Here we report that a single immunization with Ad26.M.Env ZIKV vaccine, when administered prior to conception, fully protects pregnant rhesus macaques from ZIKV viral RNA in blood and tissues with no adverse effects in dams and fetuses. Furthermore, vaccination prevents ZIKV distribution to fetal tissues including the brain. ZIKV associated neuropathology was absent in offspring of Ad26.M.Env vaccinated dams, although pathology was limited in fetuses from non-immunized, challenged dams. Vaccine efficacy is associated with induction of ZIKV neutralizing antibodies in pregnant rhesus macaques. These data suggest the feasibility of vaccine prevention of CZS in humans.

Boletim epidemiológico: monitoramento dos casos de arboviroses em Goiás da semana epidemiológica 01 a 27 de 2024 / Epidemiological bulletin: monitoring of arbovirus cases in Goiás from epidemiological week 01 to 27 of 2024

As arboviroses transmitidas pelo mosquito Aedes aegypt são um dos principais problemas de saúde pública no Estado de Goiás. O boletim epidemiológico das arboiross tem o objetivo de apresentar a situação epidemiológica dos casos no estado, utilizando como fonte de dados os registros de casos suspeitos e confirmados ocorridos nos últimos anos, disponíveis no SINan Online e SINAN Net também são apresentados dados relativos à síndrome congênita associada à infecção peli Zika vírus, disponíveis no Sistema de Registro de Eventos em Saúde Pública (RESP) - Microcefalias

Arboviruses transmitted by the Aedes aegypt mosquito are one of the main public health problems in the State of Goiás. The arboiross epidemiological bulletin aims to present the epidemiological situation of cases in the state, using records of suspected and confirmed cases as a data source. occurred in recent years, available on SINan Online and SINAN Net, data relating to congenital syndrome associated with Zika virus infection, available on the Public Health Event Registration System (RESP) - Microcephaly, is also presented

Serious Concern of Congenital Zika Syndrome (CZS) in India: A Narrative Review.

Congenital Zika syndrome (CZS) is a major concern in India and highlights the multifaceted challenges posed by the Zika virus (ZIKV). The alarming increase in CZS cases in India, a condition that has serious effects on both public health and newborns, has raised concerns. This review highlights the importance of raising concern and awareness and taking preventive measures by studying the epidemiology, clinical symptoms, and potential long-term consequences of CZS. The review also contributes to worldwide research and information sharing to improve the understanding and prevention of CZS. As India deals with the changing nature of CZS, this thorough review is an important tool for policymakers, health workers, and researchers to understand what is happening now, plan for what to do in the future, and work together as a team, using medical knowledge, community involvement, and study projects to protect newborns' health and reduce the public health impact of these syndromes.

Pregnant women's perceptions on Information Sources on Zika Virus: a qualitative study.

The Zika virus (ZIKV) epidemic had a sanitary, psychosocial, and economic impact on individuals of reproductive age. The primary concern revolved around infection during pregnancy due to possible vertical transmission and its association with adverse fetal and infant outcomes, known as Congenital Zika Syndrome (CZS). This qualitative study employs phenomenology and grounded theory. This study includes interviews with 98 women, some pregnant during the ZIKV epidemic in Brazil, Colombia, and Puerto Rico, who had children with CZS or without diagnosed neurological impairment. Additionally, the study included a group of women who were pregnant during the COVID-19 pandemic in these same countries. In both groups, interviewees had varying levels of knowledge about ZIKV. The study found that messages conveyed through the media tended to be alarmist, in contrast to the information provided by healthcare professionals, which was considered more trustworthy. Pregnant women during the ZIKV epidemic reported receiving their ZIKV and CSZ infection diagnoses late, either during or after childbirth. The study underscores the needs of pregnant women in high-risk scenarios, the importance of health education processes, and the necessity to reinforce communication and continuing education.

A epidemia do vírus Zika (ZIKV) teve impacto sanitário, psicossocial e econômico sobre pessoas em idade reprodutiva. A principal preocupação foi a infecção durante a gravidez devido a possível transmissão vertical e sua associação com resultados fetais e infantis adversos, conhecida como síndrome congênita associada à infecção pelo Vírus Zika (SCZ). Este estudo qualitativo utiliza a fenomenologia e a teoria fundamentada. O estudo inclui entrevistas com 98 mulheres, parte grávida durante a epidemia de ZIKV no Brasil, Colômbia e Porto Rico e que tiveram filhos com SCZ ou sem comprometimento neurológico diagnosticado. Além disso, o estudo inclui um grupo de mulheres grávidas durante a pandemia de COVID-19 nos mesmos países. Em ambos os grupos, as entrevistadas tinham diferentes níveis de conhecimento sobre ZIKV. O estudo constatou que as mensagens veiculadas por meio da mídia eram alarmistas; em contraste com as informações fornecidas por profissionais de saúde, consideradas mais confiáveis. Mulheres gestantes durante a epidemia do ZIKV relataram ter recebido seu diagnóstico de infecção por ZIKV e SCZ tardiamente ou após o parto. O estudo destaca as necessidades das mulheres grávidas em cenários de alto risco, a importância de processos de educação em saúde e a necessidade de reforçar a comunicação e a educação continuada.

Clinical spectrum of congenital Zika virus infection in Brazil: Update and issues for research development.

This review aimed to provide an update on the morphological and/or functional abnormalities related to congenital Zika virus (ZIKV) infection, based on primary data from studies conducted in Brazil since 2015. During the epidemic years (2015-2016), case series and pediatric cohort studies described several birth defects, including severe and/or disproportionate microcephaly, cranial bone overlap, skull collapse, congenital contractures (arthrogryposis and/or clubfoot), and visual and hearing abnormalities, as part of the spectrum of Congenital Zika Syndrome (CZS). Brain imaging abnormalities, mainly cortical atrophy, ventriculomegaly, and calcifications, serve as structural markers of CZS severity. Most case series and cohorts of microcephaly have reported the co-occurrence of epilepsy, dysphagia, orthopedic deformities, motor function impairment, cerebral palsy, and urological impairment. A previous large meta-analysis conducted in Brazil revealed that a confirmed ZIKV infection during pregnancy was associated with a 4% risk of microcephaly. Additionally, one-third of children showed at least one abnormality, predominantly identified in isolation. Studies examining antenatally ZIKV-exposed children without detectable abnormalities at birth reported conflicting neurodevelopmental results. Therefore, long-term follow-up studies involving pediatric cohorts with appropriate control groups are needed to address this knowledge gap. We recognize the crucial role of a national network of scientists collaborating with international research institutions in understanding the lifelong consequences of congenital ZIKV infection. Additionally, we highlight the need to provide sustainable resources for research and development to reduce the risk of future Zika outbreaks.

Feeding practices and weight status of children with congenital Zika syndrome: A longitudinal study in Brazil.

OBJECTIVE: The objective of this study was to describe feeding practices and weight status in a cohort of children with congenital Zika syndrome (CZS) in northeastern Brazil. METHODS: This longitudinal study of children with CZS (N = 156) included data collection on child feeding practices and weight status at five timepoints between 2018 and 2022. The average age of the children was 32.1 months at enrollment and 76.6 months at the fifth assessment. Multilevel models, with repeated observations nested within children, were used to estimate time-related differences in each outcome. RESULTS: Use of enteral feeding, such as gastrostomy, increased from 19.2% to 33.3% over 4 years (p < .001). Among children who did not exclusively use an enteral feeding method, the percentage experiencing at least one dysphagia-associated behavior, such as coughing or gagging, increased from 73.9% to 85.3% (p = .030) while consuming liquids and from 36.2% to 73.5% (p = .001) while consuming solids. Based on weight-for-age z-scores, the percentage of children who were moderately or severely underweight increased from 42.5% to 46.1% over the 4 years but was not statistically significant. Children exclusively using an enteral feeding method had significantly decreased odds of being underweight at assessments 3, 4, and 5. CONCLUSIONS: These data highlight the ongoing and increasing challenges of feeding young children with CZS. Our findings elucidate the physiological reasons children with CZS may be underweight and point to intervention targets, such as enteral feeding, to improve their feeding practices.

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.

Zika Virus Neuropathogenesis-Research and Understanding.

Zika virus (ZIKV), a mosquito-borne flavivirus, is prominently associated with microcephaly in babies born to infected mothers as well as Guillain-Barré Syndrome in adults. Each cell type infected by ZIKV-neuronal cells (radial glial cells, neuronal progenitor cells, astrocytes, microglia cells, and glioblastoma stem cells) and non-neuronal cells (primary fibroblasts, epidermal keratinocytes, dendritic cells, monocytes, macrophages, and Sertoli cells)-displays its own characteristic changes to their cell physiology and has various impacts on disease. Here, we provide an in-depth review of the ZIKV life cycle and its cellular targets, and discuss the current knowledge of how infections cause neuropathologies, as well as what approaches researchers are currently taking to further advance such knowledge. A key aspect of ZIKV neuropathogenesis is virus-induced neuronal apoptosis via numerous mechanisms including cell cycle dysregulation, mitochondrial fragmentation, ER stress, and the unfolded protein response. These, in turn, result in the activation of p53-mediated intrinsic cell death pathways. A full spectrum of infection models including stem cells and co-cultures, transwells to simulate blood-tissue barriers, brain-region-specific organoids, and animal models have been developed for ZIKV research.

Infection by zika virus increase angiotensin I-converting enzyme activity in mouse brain.

Congenital zika virus syndrome (CZS) has become a significant worldwide concern since the sudden rise of microcephaly related to zika virus (ZIKV) in Brazil. Primarily transmitted by Aedes mosquitoes, ZIKV shares serologic similarities with dengue virus (DENV), complicating the diagnosis and/or clinical management. The Angiotensin I-Converting Enzyme (ACE) was associated with either neuroprotective or anti-inflammatory properties in the central nervous system (CNS). The possible role(s) of ACE in these two flaviviruses infection remain largely unexplored. In this study, we evaluate ACE activity in the brain of ZIKV- or DENV-infected mice, both compared to MOCK, showing about 30 % increased ACE activity only in ZIKV-infected mice (p = 0.024), while no change was noticed in brain from DENV-infected animals (p = 0.888). In addition, the treatment with interferon beta (IFNß), under conditions previously demonstrated to rescue the normal size of microcephalic brains determined by ZIKV infection, also restored ACE activity in ZIKV-infected animals to levels close to that of the MOCK control group. Although inflammatory responses expected for either ZIKV or DENV infections, only ZIKV was associated with microcephaly, as well as with increased ACE activity and reversion by treatment with IFNß. Furthermore, this increase in ACE activity was observed only after intracerebroventricular (ICV) injection (F (2, 16) = 7.907, p = 0.004), but not for intraperitoneal (IP) administration of ZIKV (F (2, 26) = 1.996, p = 0.156), suggesting that the observed central ACE activity modulation may be associated with the presence of this specific flavivirus in the brain.

Testicular damage without clinical manifestations in BALB/c mice experimentally infected with Zika virus.

In 2015-2016, the Zika virus (ZIKV) caused a major epidemic in the Americas, increasing cases of microcephaly and Guillain-Barré syndrome. During this period, the discovery of ZIKV sexual transmission intensified studies on the impact of this virus on the reproductive organs. For this study, 2-month-old male BALB/c mice were infected with 1.26 x 106 PFU/mL of ZIKV in solution via the intravenous route. After three, seven, and fourteen days post-infection (DPI), blood and testicle samples were obtained to detect ZIKV RNA. The authors observed that the infected animals had slower weight gain than the control group. Viremia occurred only at 3DPI, and the ZIKV RNA was detected in one testis sample at 7DPI. The histopathological analysis of this organ revealed intense disorganization of the seminiferous tubules' structure, inflammatory infiltrate, necrosis, hemorrhage, fluid accumulation, congestion of blood vessels, and reduced sperm count. Ultrastructural analysis showed nuclear changes in tubule cells, activation of interstitial cells, and morphological changes in spermatozoa, in addition to fragmentation and decreased electron density of the genetic material of these cells. Thus, despite causing predominantly asymptomatic infections, ZIKV can cause significant subclinical and transient damage, including to male reproductive organs.